For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 56376). This missense change has been observed in individual(s) with lysinuric protein intolerance (PMID: 12402335, 31427715). It is commonly reported in individuals of Japanese ancestry (PMID: 26865117). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 238 of the SLC7A7 protein (p.Ser238Phe).
ClinVar Genomic variation as it relates to human health
NM_003982.4(SLC7A7):c.713C>T (p.Ser238Phe)
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.
(6)
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
6
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_003982.4(SLC7A7):c.713C>T (p.Ser238Phe)
Variation ID: 56376 Accession: VCV000056376.12
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 14q11.2 14: 22778850 (GRCh38) [ NCBI UCSC ] 14: 23248059 (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 Jul 24, 2013 Jun 17, 2024 Dec 10, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_003982.4:c.713C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003973.3:p.Ser238Phe missense NM_001126105.3:c.713C>T NP_001119577.1:p.Ser238Phe missense NM_001126106.4:c.713C>T NP_001119578.1:p.Ser238Phe missense NC_000014.9:g.22778850G>A NC_000014.8:g.23248059G>A NG_012851.2:g.55971C>T LRG_695:g.55971C>T LRG_695t1:c.713C>T LRG_695p1:p.Ser238Phe LRG_695t2:c.713C>T LRG_695p2:p.Ser238Phe LRG_695t3:c.713C>T LRG_695p3:p.Ser238Phe Q9UM01:p.Ser238Phe - Protein change
- S238F
- Other names
- -
- Canonical SPDI
- NC_000014.9:22778849:G:A
-
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. |
|||
| SLC7A7 | - | - |
GRCh38 GRCh37 |
756 | 821 | |
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 (5) |
criteria provided, multiple submitters, no conflicts
|
Dec 10, 2023 | RCV000049789.12 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
May 9, 2022 | RCV002307385.2 |
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
(Sep 08, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001228753.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function … (more)
For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 56376). This missense change has been observed in individual(s) with lysinuric protein intolerance (PMID: 12402335, 31427715). It is commonly reported in individuals of Japanese ancestry (PMID: 26865117). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 238 of the SLC7A7 protein (p.Ser238Phe). (less)
|
|
|
Pathogenic
(Nov 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002045732.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
|
|
|
Pathogenic
(Dec 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005056870.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Oct 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: yes
Allele origin:
maternal
|
3billion
Accession: SCV002012236.1
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 pathogenic/likely pathogeic with strong evidence (ClinVar ID: VCV000056376.3, PMID:26865117, PS1). It … (more)
Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogeic with strong evidence (ClinVar ID: VCV000056376.3, PMID:26865117, PS1). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported to be located within a uniparental isodisomy (UPD) region of maternal chromosome 6 and (PMID: 31427715), and each parent has also been observed to be heterozygous for the variant (PMID 12402335, PM3). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.959, 3Cnet: 0.883, PP3). Patient's phenotype is considered compatible with Lysinuric protein intolerance (3billion dataset, PP4). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Failure to thrive (present) , Delayed gross motor development (present) , Delayed fine motor development (present) , Chronic diarrhea (present)
|
|
|
Likely pathogenic
(May 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002601504.2
First in ClinVar: Nov 19, 2022 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16966712, 32901917, 31427715, 26865117, Seo2019[preprint], 12402335, 17764084) (less)
|
|
|
probable-pathogenic
(-)
|
no assertion criteria provided
Method: not provided
|
Lysinuric protein intolerance
Affected status: not provided
Allele origin:
not provided
|
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082196.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
|
Comment:
Converted during submission to Likely pathogenic.
|
Comment:
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogeic with strong evidence (ClinVar ID: VCV000056376.3, PMID:26865117, PS1). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported to be located within a uniparental isodisomy (UPD) region of maternal chromosome 6 and (PMID: 31427715), and each parent has also been observed to be heterozygous for the variant (PMID 12402335, PM3). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.959, 3Cnet: 0.883, PP3). Patient's phenotype is considered compatible with Lysinuric protein intolerance (3billion dataset, PP4). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16966712, 32901917, 31427715, 26865117, Seo2019[preprint], 12402335, 17764084)
Comment:
Converted during submission to Likely pathogenic.
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:
For these reasons, this variant has been classified as Pathogenic. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 56376). This missense change has been observed in individual(s) with lysinuric protein intolerance (PMID: 12402335, 31427715). It is commonly reported in individuals of Japanese ancestry (PMID: 26865117). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 238 of the SLC7A7 protein (p.Ser238Phe).
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogeic with strong evidence (ClinVar ID: VCV000056376.3, PMID:26865117, PS1). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported to be located within a uniparental isodisomy (UPD) region of maternal chromosome 6 and (PMID: 31427715), and each parent has also been observed to be heterozygous for the variant (PMID 12402335, PM3). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.959, 3Cnet: 0.883, PP3). Patient's phenotype is considered compatible with Lysinuric protein intolerance (3billion dataset, PP4). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16966712, 32901917, 31427715, 26865117, Seo2019[preprint], 12402335, 17764084)
Comment:
Converted during submission to Likely pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Lysinuric protein intolerance with homozygous SLC7A7 mutation caused by maternal uniparental isodisomy of chromosome 14. | Kang E | Journal of human genetics | 2019 | PMID: 31427715 |
| Clinical and genetic features of lysinuric protein intolerance in Japan. | Noguchi A | Pediatrics international : official journal of the Japan Pediatric Society | 2016 | PMID: 26865117 |
| Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance. | Shoji Y | Human mutation | 2002 | PMID: 12402335 |
Text-mined citations for rs386833823 ...
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 Sep 29, 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.