ClinVar Genomic variation as it relates to human health
NM_033409.4(SLC52A3):c.639C>G (p.Tyr213Ter)
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_033409.4(SLC52A3):c.639C>G (p.Tyr213Ter)
Variation ID: 210018 Accession: VCV000210018.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20p13 20: 763932 (GRCh38) [ NCBI UCSC ] 20: 744576 (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 Oct 5, 2015 Oct 8, 2024 May 10, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_033409.4:c.639C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_212134.3:p.Tyr213Ter nonsense NM_001370085.1:c.639C>G NP_001357014.1:p.Tyr213Ter nonsense NM_001370086.1:c.639C>G NP_001357015.1:p.Tyr213Ter nonsense NC_000020.11:g.763932G>C NC_000020.10:g.744576G>C NG_027687.2:g.17054C>G LRG_1394:g.17054C>G LRG_1394t1:c.639C>G LRG_1394p1:p.Tyr213Ter - Protein change
- Y213*
- Other names
- Tyr213X
- Canonical SPDI
- NC_000020.11:763931:G: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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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00004
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
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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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SLC52A3 | - | - |
GRCh38 GRCh37 |
440 | 504 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (3) |
criteria provided, single submitter
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Jan 29, 2024 | RCV000191963.9 | |
Pathogenic (1) |
criteria provided, single submitter
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May 4, 2022 | RCV002247619.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 29, 2020 | RCV002354538.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 10, 2024 | RCV003313053.9 |
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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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Progressive bulbar palsy of childhood
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002519781.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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Brown-Vialetto-van Laere syndrome 1
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001209505.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr213*) in the SLC52A3 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Tyr213*) in the SLC52A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC52A3 are known to be pathogenic (PMID: 20206331, 22824638, 25462087). This variant is present in population databases (rs778363575, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with Brown-Vialetto-Van Laere syndrome (PMID: 20206331, 21110228, 23688382). ClinVar contains an entry for this variant (Variation ID: 210018). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Oct 29, 2020)
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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: SCV002655312.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.Y213* pathogenic mutation (also known as c.639C>G), located in coding exon 2 of the SLC52A3 gene, results from a C to G substitution at … (more)
The p.Y213* pathogenic mutation (also known as c.639C>G), located in coding exon 2 of the SLC52A3 gene, results from a C to G substitution at nucleotide position 639. This changes the amino acid from a tyrosine to a stop codon within coding exon 2. This alteration has been reported in the homozygous state and in the compound heterozygous state with other variants in SLC52A3 in multiple individuals with Brown-Vialetto-Van Laere syndrome (Bosch AM et al. J Inherit Metab Dis, 2011 Feb;34:159-64; Green P et al. Am J Hum Genet, 2010 Mar;86:485-9; Johnson JO et al. Am J Hum Genet, 2010 Oct;87:567-9; author reply 569-70; Malafronte P et al. Pediatr Dev Pathol May;16:364-71). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(May 10, 2024)
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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: SCV004012563.3
First in ClinVar: Jul 16, 2023 Last updated: Sep 29, 2024 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23688382, 31980526, 34490615, 32773395, 34662687, 31959559, 26444347, 29961494, 25462087, 21110228, 20920669, 22824638, 26072523, 20206331) (less)
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Pathogenic
(Mar 01, 2024)
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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: SCV004811467.6
First in ClinVar: Apr 15, 2024 Last updated: Oct 08, 2024 |
Comment:
SLC52A3: PVS1, PM2, PM3
Number of individuals with the variant: 1
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Pathogenic
(Feb 01, 2011)
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no assertion criteria provided
Method: literature only
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BROWN-VIALETTO-VAN LAERE SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000045313.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 23, 2016 |
Comment on evidence:
In a patient with Brown-Vialetto-Van Laere syndrome (BVVLS1; 211530), Bosch et al. (2011) identified compound heterozygosity for a C-to-G transversion at nucleotide 639 of the … (more)
In a patient with Brown-Vialetto-Van Laere syndrome (BVVLS1; 211530), Bosch et al. (2011) identified compound heterozygosity for a C-to-G transversion at nucleotide 639 of the C20ORF54 gene, resulting in a tyrosine-to-termination substitution at codon 213 (Y213X), and a missense mutation (W17R; 613350.0009). The nonsense mutation had been identified by Green et al. (2010). (less)
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not provided
(-)
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no classification provided
Method: literature only
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Brown-Vialetto-van Laere syndrome 1
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000246217.2
First in ClinVar: Oct 05, 2015 Last updated: Oct 01, 2022 |
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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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Riboflavin Transporter Deficiency. | Adam MP | - | 2021 | PMID: 26072523 |
Adult onset Brown-Vialetto-Van Laere syndrome with opsoclonus and a novel heterozygous mutation: a case report. | Cosgrove J | Clinical neurology and neurosurgery | 2015 | PMID: 25462087 |
Brown-Vialetto-Van Laere syndrome: clinical and neuropathologic findings with immunohistochemistry for C20orf54 in three affected patients. | Malafronte P | Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society | 2013 | PMID: 23688382 |
Brown-Vialetto-van Laere and Fazio-Londe overlap syndromes: a clinical, biochemical and genetic study. | Ciccolella M | Neuromuscular disorders : NMD | 2012 | PMID: 22824638 |
Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. | Bosch AM | Journal of inherited metabolic disease | 2011 | PMID: 21110228 |
Exome sequencing in Brown-Vialetto-van Laere syndrome. | Johnson JO | American journal of human genetics | 2010 | PMID: 20920669 |
Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. | Green P | American journal of human genetics | 2010 | PMID: 20206331 |
Text-mined citations for rs778363575 ...
HelpRecord last updated Oct 08, 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.