ClinVar Genomic variation as it relates to human health
NM_001039141.3(TRIOBP):c.5705A>C (p.Lys1902Thr)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001039141.3(TRIOBP):c.5705A>C (p.Lys1902Thr)
Variation ID: 229363 Accession: VCV000229363.35
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 22q13.1 22: 37757630 (GRCh38) [ NCBI UCSC ] 22: 38153637 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 9, 2018 Oct 20, 2024 Aug 9, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001039141.3:c.5705A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001034230.1:p.Lys1902Thr missense NM_007032.5:c.566A>C NP_008963.3:p.Lys189Thr missense NM_138632.2:c.566A>C NP_619538.2:p.Lys189Thr missense NC_000022.11:g.37757630A>C NC_000022.10:g.38153637A>C NG_012857.1:g.65643A>C - Protein change
- K1902T, K189T
- Other names
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- Canonical SPDI
- NC_000022.11:37757629:A:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00020 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00054
The Genome Aggregation Database (gnomAD), exomes 0.00062
The Genome Aggregation Database (gnomAD) 0.00071
Trans-Omics for Precision Medicine (TOPMed) 0.00073
Exome Aggregation Consortium (ExAC) 0.00133
- 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 | ||
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HI score
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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. |
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TRIOBP | - | - |
GRCh38 GRCh37 |
844 | 938 |
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. |
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Uncertain significance (1) |
criteria provided, single submitter
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Nov 10, 2020 | RCV000219620.9 | |
Uncertain significance (7) |
criteria provided, multiple submitters, no conflicts
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Aug 9, 2022 | RCV000727151.27 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000765639.3 | |
TRIOBP-related disorder
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Uncertain significance (1) |
no assertion criteria provided
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Feb 15, 2024 | RCV003929911.2 |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 17, 2021 | RCV004020639.1 |
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. |
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Uncertain significance
(Apr 25, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000706169.2
First in ClinVar: May 29, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Nov 10, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000272558.4
First in ClinVar: May 29, 2016 Last updated: May 29, 2021 |
Comment:
Variant classified as Uncertain Significance - Favor Benign. The p.Lys1902Thr variant in TRIOBP has been reported by our laboratory in six individuals with sensorineural hearing … (more)
Variant classified as Uncertain Significance - Favor Benign. The p.Lys1902Thr variant in TRIOBP has been reported by our laboratory in six individuals with sensorineural hearing loss. None of these individuals carried a second pathogenic variant in TRIOBP gene, and two individuals had an alternate etiology identified. It has been identified in 0.1% (31/26602) of South Asian chromosomes and 0.09% (99/105770) of European chromosomes including 1 homozygote by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs138804394). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant has also been reported in ClinVar (Variation ID 229363). Computational prediction tools and conservation analysis suggest that the p.Lys1902Thr variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while the clinical significance of the p.Lys1902Thr variant is uncertain, its frequency suggests it is more likely to be benign. ACMG/AMP Criteria applied: PP3, BS1_Supporting. (less)
Number of individuals with the variant: 6
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Uncertain significance
(Jul 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001764301.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our … (more)
In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) (less)
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Uncertain significance
(Aug 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003257423.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 1902 of the TRIOBP protein (p.Lys1902Thr). … (more)
This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 1902 of the TRIOBP protein (p.Lys1902Thr). This variant is present in population databases (rs138804394, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with TRIOBP-related conditions. ClinVar contains an entry for this variant (Variation ID: 229363). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 28
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000896968.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Uncertain significance
(Apr 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004225608.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
BS1_supporting
Number of individuals with the variant: 1
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Uncertain significance
(Aug 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV004971572.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.5705A>C (p.K1902T) alteration is located in exon 16 (coding exon 14) of the TRIOBP gene. This alteration results from a A to C substitution … (more)
The c.5705A>C (p.K1902T) alteration is located in exon 16 (coding exon 14) of the TRIOBP gene. This alteration results from a A to C substitution at nucleotide position 5705, causing the lysine (K) at amino acid position 1902 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Aug 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002585930.15
First in ClinVar: Oct 22, 2022 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001959285.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001975845.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Uncertain significance
(Feb 15, 2024)
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no assertion criteria provided
Method: clinical testing
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TRIOBP-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004747812.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
The TRIOBP c.5705A>C variant is predicted to result in the amino acid substitution p.Lys1902Thr. To our knowledge, this variant has not been reported in the … (more)
The TRIOBP c.5705A>C variant is predicted to result in the amino acid substitution p.Lys1902Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.12% of alleles in individuals of South Asian descent in gnomAD, including one homozygote. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TRIOBP | - | - | - | - |
Text-mined citations for rs138804394 ...
HelpRecord last updated Oct 20, 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.