ClinVar Genomic variation as it relates to human health
NM_003072.5(SMARCA4):c.38G>T (p.Arg13Leu)
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_003072.5(SMARCA4):c.38G>T (p.Arg13Leu)
Variation ID: 1942941 Accession: VCV001942941.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 10984189 (GRCh38) [ NCBI UCSC ] 19: 11094865 (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 Feb 7, 2023 Feb 28, 2024 Dec 26, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003072.5:c.38G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003063.2:p.Arg13Leu missense NM_001387283.1:c.38G>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001374212.1:p.Arg13Leu missense NM_001128844.3:c.38G>T NP_001122316.1:p.Arg13Leu missense NM_001128845.2:c.38G>T NP_001122317.1:p.Arg13Leu missense NM_001128846.2:c.38G>T NP_001122318.1:p.Arg13Leu missense NM_001128847.4:c.38G>T NP_001122319.1:p.Arg13Leu missense NM_001128848.2:c.38G>T NP_001122320.1:p.Arg13Leu missense NM_001128849.1:c.38G>T NM_001128849.3:c.38G>T NP_001122321.1:p.Arg13Leu missense NM_001374457.1:c.38G>T NP_001361386.1:p.Arg13Leu missense NM_001411150.1:c.38G>T NP_001398079.1:p.Arg13Leu missense NR_164683.1:n.214G>T non-coding transcript variant NC_000019.10:g.10984189G>T NC_000019.9:g.11094865G>T NG_011556.3:g.28258G>T LRG_878:g.28258G>T LRG_878t1:c.38G>T LRG_878p1:p.Arg13Leu - Protein change
- R13L
- Other names
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- Canonical SPDI
- NC_000019.10:10984188:G:T
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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.
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- 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
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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
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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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SMARCA4 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5482 | 5505 |
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
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Dec 26, 2023 | RCV002647057.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 2, 2023 | RCV003167587.2 |
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
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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
(Aug 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003855189.2
First in ClinVar: Apr 15, 2023 Last updated: Oct 28, 2023 |
Comment:
The p.R13L variant (also known as c.38G>T), located in coding exon 1 of the SMARCA4 gene, results from a G to T substitution at nucleotide … (more)
The p.R13L variant (also known as c.38G>T), located in coding exon 1 of the SMARCA4 gene, results from a G to T substitution at nucleotide position 38. The arginine at codon 13 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Missense and in-frame variants in SMARCA4 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome including small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Jelinic P et al. Nat Genet. 2014 May;46(5):424-6). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Aug 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Rhabdoid tumor predisposition syndrome 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004204939.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain significance
(Dec 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Rhabdoid tumor predisposition syndrome 2
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002983906.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 13 of the SMARCA4 protein (p.Arg13Leu). … (more)
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 13 of the SMARCA4 protein (p.Arg13Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1942941). 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 SMARCA4 protein function with a negative predictive value of 95%. 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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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Mar 05, 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.