Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002433548 | SCV002746333 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-10 | criteria provided, single submitter | clinical testing | The p.T93A variant (also known as c.277A>G), located in coding exon 5 of the BAP1 gene, results from an A to G substitution at nucleotide position 277. The threonine at codon 93 is replaced by alanine, an amino acid with similar properties. This alteration was shown to segregate with renal cell carcinoma in a French family (Popova T et al. Am J Hum Genet, 2013 Jun;92:974-80). RNA studies have demonstrated that this alteration causes abnormal splicing resulting in a transcript predicted to undergo nonsense-mediated decay (Ambry internal data; Popova T et al. Am J Hum Genet, 2013 Jun;92:974-80). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000049290 | SCV004293103 | uncertain significance | BAP1-related tumor predisposition syndrome | 2022-12-03 | criteria provided, single submitter | clinical testing | 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 expected to disrupt BAP1 protein function. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 55879). This missense change has been observed in individual(s) with renal cell carcinoma and cervix carcinoma (PMID: 23684012). This variant is present in population databases (rs375129361, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 93 of the BAP1 protein (p.Thr93Ala). |
| OMIM | RCV000049290 | SCV000077547 | pathogenic | BAP1-related tumor predisposition syndrome | 2013-06-06 | no assertion criteria provided | literature only |