ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.1633C>T (p.Arg545Cys)

gnomAD frequency: 0.00001  dbSNP: rs778628881
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472985 SCV000553949 uncertain significance BAP1-related tumor predisposition syndrome 2023-04-12 criteria provided, single submitter clinical testing 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. 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 BAP1 protein function. ClinVar contains an entry for this variant (Variation ID: 412423). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. This variant is present in population databases (rs778628881, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 545 of the BAP1 protein (p.Arg545Cys).
Color Diagnostics, LLC DBA Color Health RCV001805082 SCV002052258 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-17 criteria provided, single submitter clinical testing This missense variant replaces arginine with cysteine at codon 545 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 1/251146 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.
Ambry Genetics RCV001805082 SCV002702989 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-03 criteria provided, single submitter clinical testing The p.R545C variant (also known as c.1633C>T), located in coding exon 13 of the BAP1 gene, results from a C to T substitution at nucleotide position 1633. The arginine at codon 545 is replaced by cysteine, an amino acid with highly dissimilar properties. 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.
Baylor Genetics RCV000472985 SCV004213161 uncertain significance BAP1-related tumor predisposition syndrome 2023-10-31 criteria provided, single submitter clinical testing

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