ClinVar Genomic variation as it relates to human health
NM_012434.5(SLC17A5):c.291G>A (p.Thr97=)
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
-
NM_012434.5(SLC17A5):c.291G>A (p.Thr97=)
Variation ID: 56554 Accession: VCV000056554.13
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 6q13 6: 73644407 (GRCh38) [ NCBI UCSC ] 6: 74354130 (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 Mar 21, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_012434.5:c.291G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_036566.1:p.Thr97= synonymous NC_000006.12:g.73644407C>T NC_000006.11:g.74354130C>T NG_008272.1:g.14608G>A - Protein change
- Other names
- p.Thr97=
- Canonical SPDI
- NC_000006.12:73644406: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.
The Genome Aggregation Database (gnomAD) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
Exome Aggregation Consortium (ExAC) 0.00002
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. |
|||
SLC17A5 | - | - |
GRCh38 GRCh37 |
564 | 661 |
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 (6) |
criteria provided, multiple submitters, no conflicts
|
Mar 21, 2024 | RCV000049967.10 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Aug 24, 2022 | RCV000426686.3 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Sep 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Salla disease
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000794171.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013 |
|
|
Likely pathogenic
(May 28, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000517211.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual … (more)
In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20101035, 25085675, 15172001, 28662915, 28771251) (less)
|
|
Likely pathogenic
(Sep 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Salla disease
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002027581.1
First in ClinVar: Nov 29, 2021 Last updated: Nov 29, 2021 |
|
|
Likely pathogenic
(Aug 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004226560.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP4, PM2, PM3_strong
Number of individuals with the variant: 1
|
|
Pathogenic
(Dec 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Salla disease
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001588446.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects codon 97 of the SLC17A5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid … (more)
This sequence change affects codon 97 of the SLC17A5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SLC17A5 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs386833990, gnomAD 0.004%). This variant has been observed in individual(s) with free sialic acid storage disease (PMID: 28662915, 28771251). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56554). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in deletion of the 197 bases of exon 2 and introduces a premature termination codon (PMID: 15172001). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Mar 21, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Salla disease
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004201212.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Salla disease
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001453516.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
probable-pathogenic
(-)
|
no assertion criteria provided
Method: not provided
|
Salla disease
Affected status: not provided
Allele origin:
not provided
|
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082376.1
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.
|
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 |
---|---|---|---|---|
Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. | Lionel AC | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 28771251 |
A New Patient With Intermediate Severe Salla Disease With Hypomyelination: A Literature Review for Salla Disease. | Barmherzig R | Pediatric neurology | 2017 | PMID: 28662915 |
Abstracts of the SSIEM 2014 Annual Symposium, 2-5 September, 2014, Innsbruck, Austria. | - | Journal of inherited metabolic disease | 2014 | PMID: 25085675 |
Elevated CSF N-acetylaspartylglutamate in patients with free sialic acid storage diseases. | Mochel F | Neurology | 2010 | PMID: 20101035 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity. | Kleta R | Molecular genetics and metabolism | 2004 | PMID: 15172001 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs386833990 ...
HelpRecord last updated Jun 17, 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.