Pathogenic variant based on genotype/phenotype relationship. This patient has been reported in PMID 28132692.
ClinVar Genomic variation as it relates to human health
NM_052876.4(NACC1):c.892C>T (p.Arg298Trp)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(13)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
13
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_052876.4(NACC1):c.892C>T (p.Arg298Trp)
Variation ID: 417784 Accession: VCV000417784.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19p13.13 19: 13136099 (GRCh38) [ NCBI UCSC ] 19: 13246913 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 23, 2017 Oct 26, 2024 Jun 29, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_052876.4:c.892C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_443108.1:p.Arg298Trp missense NC_000019.10:g.13136099C>T NC_000019.9:g.13246913C>T - Protein change
- R298W
- Other names
- -
- Canonical SPDI
- NC_000019.10:13136098:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| NACC1 | - | - |
GRCh38 GRCh37 |
420 | 453 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Jun 29, 2023 | RCV000477683.12 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 14, 2023 | RCV000522576.11 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
Jun 7, 2017 | RCV000624692.2 | |
|
NACC1-related disorder
|
not provided (1) |
no classification provided
|
- | RCV001824794.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Feb 02, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Undiagnosed Diseases Network, NIH
Accession: SCV000622158.2
First in ClinVar: Apr 23, 2017 Last updated: Apr 23, 2017 |
Comment:
Pathogenic variant based on genotype/phenotype relationship. This patient has been reported in PMID 28132692.
Clinical Features:
Webbed penis (present) , Toenail dysplasia (present) , Thick eyebrow (present) , Single transverse palmar crease (present) , Short stature (present) , Short philtrum (present) … (more)
Webbed penis (present) , Toenail dysplasia (present) , Thick eyebrow (present) , Single transverse palmar crease (present) , Short stature (present) , Short philtrum (present) , Short neck (present) , Scoliosis (present) , Profound global developmental delay (present) , Postnatal microcephaly (present) , Poor suck (present) , Pectus excavatum (present) , Oral-pharyngeal dysphagia (present) , Midface retrusion (present) , Long eyelashes (present) , Lamellar cataract (present) , Irritability (present) , Intellectual disability, moderate (present) , Infantile spasms (present) , Generalized myoclonic seizures (present) , Generalized hypotonia (present) , Gastroesophageal reflux (present) , Failure to thrive in infancy (present) , Exaggerated cupid's bow (present) , Echogenic intracardiac focus (present) , Depressed nasal bridge (present) , Delayed myelination (present) , Cortical visual impairment (present) , Clinodactyly of the 5th finger (present) , Central sleep apnea (present) , Breathing dysregulation (present) , Brachycephaly (present) (less)
Family history: no
Age: 0-9 years
Sex: male
Ethnicity/Population group: White
Testing laboratory: GeneDx
Date variant was reported to submitter: 2017-02-02
|
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447350.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Microcephaly (present) , Strabismus (present) , Global developmental delay (present) , Cerebral hypomyelination (present)
Sex: female
|
|
|
Pathogenic
(Oct 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002011957.1
First in ClinVar: Nov 11, 2021 Last updated: Nov 11, 2021 |
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported as de novoo and observed in at least four similarly affected unrelated … (more)
Same nucleotide change resulting in same amino acid change has been previously reported as de novoo and observed in at least four similarly affected unrelated individuals (PMID: 28132692, PS2 and PS4). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hypertonia (present) , Global developmental delay (present) , Inborn mitochondrial myopathy (present) , Spasticity (present) , Microcephaly (present) , Intellectual disability (present) , Cataract (present) … (more)
Hypertonia (present) , Global developmental delay (present) , Inborn mitochondrial myopathy (present) , Spasticity (present) , Microcephaly (present) , Intellectual disability (present) , Cataract (present) , Growth delay (present) , Congenital muscular dystrophy (present) , Delayed speech and language development (present) , Gastrointestinal obstruction (present) , Short stature (present) , Failure to thrive (present) , Intestinal pseudo-obstruction (present) , Polymicrogyria (present) , Intellectual disability (present) , Delayed gross motor development (present) (less)
|
|
|
Likely pathogenic
(Jun 07, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000740687.3
First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023 |
Number of individuals with the variant: 1
Sex: male
Ethnicity/Population group: Caucasian
|
|
|
Pathogenic
(Feb 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000617944.2
First in ClinVar: Dec 19, 2017 Last updated: Mar 04, 2023 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated … (more)
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31231135, 31628766, 30842647, 31036916, 31216405, 28132692, 34869110) (less)
|
|
|
Pathogenic
(Dec 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV000992791.2
First in ClinVar: Sep 21, 2019 Last updated: Mar 11, 2023 |
|
|
|
Pathogenic
(Jun 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002018190.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(May 19, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001580866.4
First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024 |
Comment:
Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change … (more)
Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has been reported to be de novo in seven individuals characterized by infantile epilepsy, cataracts, profound developmental delay, and a variety of other findings (PMID: 28132692). ClinVar contains an entry for this variant (Variation ID: 417784). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 298 of the NACC1 protein (p.Arg298Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Likely pathogenic
(May 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
Affected status: unknown
Allele origin:
germline
|
New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV002506742.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022 |
Comment:
The c.892C>T (p.Arg298Trp) variant identified in the NACC1 gene substitutes a well conserved Arginine for Tryptophan at amino acid 298/528 (exon2/6). This variant is absent … (more)
The c.892C>T (p.Arg298Trp) variant identified in the NACC1 gene substitutes a well conserved Arginine for Tryptophan at amino acid 298/528 (exon2/6). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.027) and Benign (REVEL; score:0.3639) to the function of the canonical transcript. This variant is reported as Likely Pathogenic / Pathogenic in ClinVar (VarID:417784) and has been identified in many affected individuals in the literature [PMID:28132692; PMID:30842647]. Given its presence in many affected individuals in the literature and its absence in population databases, the c.892C>T (p.Arg298Trp) variant identified in the NACC1 gene is reported as Likely Pathogenic. (less)
Clinical Features:
Seizure (present) , Intellectual disability (present) , Developmental cataract (present) , Microcephaly (present) , Failure to thrive (present) , Torticollis (present) , Spastic diplegia (present) … (more)
Seizure (present) , Intellectual disability (present) , Developmental cataract (present) , Microcephaly (present) , Failure to thrive (present) , Torticollis (present) , Spastic diplegia (present) , Hypertonia (present) , Hypotonia (present) , Pointed chin (present) , Midface retrusion (present) , Gingival overgrowth (present) (less)
Secondary finding: no
|
|
|
Pathogenic
(Mar 28, 2017)
|
no assertion criteria provided
Method: literature only
|
NEURODEVELOPMENTAL DISORDER WITH EPILEPSY, CATARACTS, FEEDING DIFFICULTIES, AND DELAYED BRAIN MYELINATION
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000564235.1
First in ClinVar: Apr 23, 2017 Last updated: Apr 23, 2017 |
Comment on evidence:
In 7 unrelated patients with neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM; 617393), Schoch et al. (2017) identified a recurrent … (more)
In 7 unrelated patients with neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM; 617393), Schoch et al. (2017) identified a recurrent de novo heterozygous c.892C-T transition (c.892C-T, NM_052876.3) in the NACC1 gene, resulting in an arg298-to-trp (R298W) substitution at a highly conserved residue. One of the patients (patient 7) was mosaic for the mutation. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the ExAC database. However, Schoch et al. (2017) noted that a different substitution at the same codon (R298L) had been observed in 1 individual in the ExAC database and in 4 individuals in the Gnome Aggregation Database (gnomAD). Functional studies of the variant and studies of patient cells were not performed. The mutation occurred at a CpG dinucleotide. The finding of the same mutation in 7 unrelated patients with a similar phenotype was statistically significant (Bonferroni corrected p = 1.25 x 10(-14)). (less)
|
|
|
Likely pathogenic
(Jun 01, 2022)
|
no assertion criteria provided
Method: provider interpretation
|
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
Affected status: yes
Allele origin:
inherited
|
Solve-RD Consortium
Accession: SCV005091455.1
First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024
Comment:
Variant identified during reanalysis of unsolved cases by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and … (more)
Variant identified during reanalysis of unsolved cases by the Solve-RD project. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257. (less)
|
Comment:
Variant confirmed as disease-causing by referring clinical team
|
|
|
Pathogenic
(May 11, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination
Affected status: yes
Allele origin:
unknown
|
Undiagnosed Diseases Network, NIH
Study: Undiagnosed Diseases Network (NIH), UDN
Accession: SCV005368705.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Number of individuals with the variant: 1
Clinical Features:
Microcephaly (present) , Cataract (present) , Upslanted palpebral fissure (present) , Hypotonia (present) , Spasticity (present) , Global developmental delay (present) , Dystonic disorder (present) … (more)
Microcephaly (present) , Cataract (present) , Upslanted palpebral fissure (present) , Hypotonia (present) , Spasticity (present) , Global developmental delay (present) , Dystonic disorder (present) , Failure to thrive (present) , Rotary nystagmus (present) , Vomiting (present) , Abnormality of extrapyramidal motor function (present) , Hyperkinetic movements (present) , Abnormal cerebral cortex morphology (present) , Abnormal muscle tone (present) , Feeding difficulties (present) , Flat face (present) , Delayed myelination (present) , Esophagitis (present) (less)
Age: 0-9 years
Sex: male
Tissue: Blood
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
NACC1-Related Disorder
Affected status: yes
Allele origin:
de novo
|
GenomeConnect, ClinGen
Accession: SCV002074832.1
First in ClinVar: Feb 12, 2022 Last updated: Feb 12, 2022 |
Comment:
Variant interpreted as Pathogenic and reported on 05-07-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Pathogenic and reported on 05-07-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Clinical Features:
Failure to thrive (present) , Abnormality of the mouth (present) , Abnormal skull morphology (present) , Abnormality of eye movement (present) , Abnormal lens morphology … (more)
Failure to thrive (present) , Abnormality of the mouth (present) , Abnormal skull morphology (present) , Abnormality of eye movement (present) , Abnormal lens morphology (present) , Abnormality of vision (present) , Sensorineural hearing loss disorder (present) , Abnormality of the nervous system (present) , Cognitive impairment (present) , Abnormality of coordination (present) , EEG abnormality (present) , Hypertonia (present) , Generalized hypotonia (present) , Movement disorder (present) , Seizure (present) , Motor stereotypies (present) , Abnormal curvature of the vertebral column (present) , Abnormality of the somatic nervous system (present) , Feeding difficulties (present) , Abnormal esophagus morphology (present) , Abnormal stomach morphology (present) , Gastrointestinal dysmotility (present) , Abnormality of the bladder (present) , Abnormality of the male genitalia (present) (less)
Indication for testing: Diagnostic
Age: 10-19 years
Sex: male
Testing laboratory: GeneDx
Date variant was reported to submitter: 2020-05-07
Testing laboratory interpretation: Pathogenic
|
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Comment:
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported as de novoo and observed in at least four similarly affected unrelated individuals (PMID: 28132692, PS2 and PS4). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31231135, 31628766, 30842647, 31036916, 31216405, 28132692, 34869110)
Comment:
Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has been reported to be de novo in seven individuals characterized by infantile epilepsy, cataracts, profound developmental delay, and a variety of other findings (PMID: 28132692). ClinVar contains an entry for this variant (Variation ID: 417784). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 298 of the NACC1 protein (p.Arg298Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.892C>T (p.Arg298Trp) variant identified in the NACC1 gene substitutes a well conserved Arginine for Tryptophan at amino acid 298/528 (exon2/6). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.027) and Benign (REVEL; score:0.3639) to the function of the canonical transcript. This variant is reported as Likely Pathogenic / Pathogenic in ClinVar (VarID:417784) and has been identified in many affected individuals in the literature [PMID:28132692; PMID:30842647]. Given its presence in many affected individuals in the literature and its absence in population databases, the c.892C>T (p.Arg298Trp) variant identified in the NACC1 gene is reported as Likely Pathogenic.
Comment:
Variant confirmed as disease-causing by referring clinical team
Comment:
Variant interpreted as Pathogenic and reported on 05-07-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Pathogenic variant based on genotype/phenotype relationship. This patient has been reported in PMID 28132692.
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported as de novoo and observed in at least four similarly affected unrelated individuals (PMID: 28132692, PS2 and PS4). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31231135, 31628766, 30842647, 31036916, 31216405, 28132692, 34869110)
Comment:
Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has been reported to be de novo in seven individuals characterized by infantile epilepsy, cataracts, profound developmental delay, and a variety of other findings (PMID: 28132692). ClinVar contains an entry for this variant (Variation ID: 417784). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 298 of the NACC1 protein (p.Arg298Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. For these reasons, this variant has been classified as Pathogenic.
Comment:
The c.892C>T (p.Arg298Trp) variant identified in the NACC1 gene substitutes a well conserved Arginine for Tryptophan at amino acid 298/528 (exon2/6). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.027) and Benign (REVEL; score:0.3639) to the function of the canonical transcript. This variant is reported as Likely Pathogenic / Pathogenic in ClinVar (VarID:417784) and has been identified in many affected individuals in the literature [PMID:28132692; PMID:30842647]. Given its presence in many affected individuals in the literature and its absence in population databases, the c.892C>T (p.Arg298Trp) variant identified in the NACC1 gene is reported as Likely Pathogenic.
Comment:
Variant confirmed as disease-causing by referring clinical team
Comment:
Variant interpreted as Pathogenic and reported on 05-07-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay. | Schoch K | American journal of human genetics | 2017 | PMID: 28132692 |
Text-mined citations for rs1060505041 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 27, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.