ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.1313C>T (p.Ser438Leu)

dbSNP: rs1443225407
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000776729 SCV000912363 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-03 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 438 of the BAP1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251430 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001361572 SCV001557550 uncertain significance BAP1-related tumor predisposition syndrome 2024-12-04 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 438 of the BAP1 protein (p.Ser438Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 630737). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BAP1 protein function with a negative predictive value of 80%. 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.
Sema4, Sema4 RCV000776729 SCV002537252 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-23 criteria provided, single submitter curation
Ambry Genetics RCV000776729 SCV002694655 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-09 criteria provided, single submitter clinical testing The p.S438L variant (also known as c.1313C>T), located in coding exon 13 of the BAP1 gene, results from a C to T substitution at nucleotide position 1313. The serine at codon 438 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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