ClinVar Genomic variation as it relates to human health
NM_004172.5(SLC1A3):c.1496G>A (p.Arg499Gln)
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.
Uncertain significance(5); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004172.5(SLC1A3):c.1496G>A (p.Arg499Gln)
Variation ID: 242994 Accession: VCV000242994.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5p13.2 5: 36686136 (GRCh38) [ NCBI UCSC ] 5: 36686238 (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 Aug 28, 2017 Apr 15, 2024 Oct 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004172.5:c.1496G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004163.3:p.Arg499Gln missense NM_001166695.3:c.1361G>A NP_001160167.1:p.Arg454Gln missense NM_001289939.2:c.1358G>A NP_001276868.1:p.Arg453Gln missense NM_001289940.2:c.1160G>A NP_001276869.1:p.Arg387Gln missense NC_000005.10:g.36686136G>A NC_000005.9:g.36686238G>A NG_015890.1:g.84782G>A - Protein change
- R454Q, R499Q, R453Q, R387Q
- Other names
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- Canonical SPDI
- NC_000005.10:36686135:G:A
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD), exomes 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00008
Exome Aggregation Consortium (ExAC) 0.00009
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
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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SLC1A3 | - | - |
GRCh38 GRCh37 |
259 | 284 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Sep 5, 2021 | RCV000234998.8 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 14, 2017 | RCV000500491.8 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Oct 1, 2023 | RCV000727383.24 |
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 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000597072.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Uncertain significance
(May 01, 2017)
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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: SCV000708035.2
First in ClinVar: Aug 28, 2017 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Jan 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Episodic ataxia type 6
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001441068.1
First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020 |
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Uncertain significance
(Sep 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Episodic ataxia type 6
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002027598.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
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Uncertain significance
(Oct 19, 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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Invitae
Accession: SCV002128034.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 499 of the SLC1A3 protein (p.Arg499Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 499 of the SLC1A3 protein (p.Arg499Gln). This variant is present in population databases (rs138085358, gnomAD 0.01%). This missense change has been observed in individual(s) with ataxia (PMID: 25497598). This variant is also known as Arg454Gln. ClinVar contains an entry for this variant (Variation ID: 242994). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC1A3 protein function. Studies have shown that this missense change alters SLC1A3 gene expression (PMID: 32741053). 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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Likely benign
(Oct 01, 2023)
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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: SCV001961875.14
First in ClinVar: Oct 08, 2021 Last updated: Apr 15, 2024 |
Comment:
SLC1A3: BS1
Number of individuals with the variant: 2
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Pathogenic
(Apr 02, 2018)
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no assertion criteria provided
Method: literature only
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EPISODIC ATAXIA, TYPE 6
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000292325.2
First in ClinVar: Jul 16, 2016 Last updated: Apr 09, 2018 |
Comment on evidence:
In 2 first cousins of European descent with a variant of episodic ataxia-6 (EA6; 612656), Pyle et al. (2015) identified a heterozygous c.1361G-A transition in … (more)
In 2 first cousins of European descent with a variant of episodic ataxia-6 (EA6; 612656), Pyle et al. (2015) identified a heterozygous c.1361G-A transition in the SLC1A3 gene, resulting in an arg454-to-gln (R454Q) substitution. The mutation, which was found by exome sequencing, was filtered against the dbSNP (build 137), 1000 Genomes Project, and Exome Sequencing Project databases, as well as 286 in-house controls. The mutation segregated with the disorder in the family. Functional studies of the variant were not performed. The patients had onset of gait ataxia and dysarthria in their thirties; the disorder was not described as episodic. (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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Functional consequences of SLC1A3 mutations associated with episodic ataxia 6. | Chivukula AS | Human mutation | 2020 | PMID: 32741053 |
Exome sequencing in undiagnosed inherited and sporadic ataxias. | Pyle A | Brain : a journal of neurology | 2015 | PMID: 25497598 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SLC1A3 | - | - | - | - |
Text-mined citations for rs138085358 ...
HelpRecord last updated Apr 15, 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.