ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.389C>T (p.Ala130Val)

dbSNP: rs1559590761
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000772609 SCV000905789 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000796958 SCV000936494 uncertain significance BAP1-related tumor predisposition syndrome 2024-10-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 130 of the BAP1 protein (p.Ala130Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with melanoma (PMID: 28062663). ClinVar contains an entry for this variant (Variation ID: 628261). 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%. Experimental studies have shown that this missense change does not substantially affect BAP1 function (PMID: 28062663). 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.
Ambry Genetics RCV000772609 SCV004001908 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-20 criteria provided, single submitter clinical testing The p.A130V variant (also known as c.389C>T), located in coding exon 6 of the BAP1 gene, results from a C to T substitution at nucleotide position 389. The alanine at codon 130 is replaced by valine, an amino acid with similar properties. In one study, this variant was identified in 1/1977 melanoma cases and 0/754 controls (O'Shea SJ et al. Hum Mol Genet, 2017 Feb;26:717-728). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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