Submissions for variant NM_004656.4(BAP1):c.55G>A (p.Val19Met)

dbSNP: rs745359087

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001178885	SCV001343447	uncertain significance	Hereditary cancer-predisposing syndrome	2019-12-03	criteria provided, single submitter	clinical testing	This missense variant replaces valine with methionine at codon 19 of the BAP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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	RCV001228580	SCV001400985	uncertain significance	BAP1-related tumor predisposition syndrome	2025-01-26	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 19 of the BAP1 protein (p.Val19Met). This variant is not present in population databases (gnomAD no frequency). 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: 920230). 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.
GeneDx	RCV003442751	SCV004170266	uncertain significance	not provided	2023-04-04	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics	RCV001228580	SCV004213242	uncertain significance	BAP1-related tumor predisposition syndrome	2023-08-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001178885	SCV005538855	uncertain significance	Hereditary cancer-predisposing syndrome	2024-10-16	criteria provided, single submitter	clinical testing	The p.V19M variant (also known as c.55G>A), located in coding exon 2 of the BAP1 gene, results from a G to A substitution at nucleotide position 55. The valine at codon 19 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.