ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.12G>A (p.Met4Ile)

dbSNP: rs1386396228
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000636072 SCV000757504 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2020-12-03 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 530294). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 4 of the BRIP1 protein (p.Met4Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine.
Sema4, Sema4 RCV002256428 SCV002531342 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-21 criteria provided, single submitter curation
Ambry Genetics RCV002256428 SCV003859926 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-01 criteria provided, single submitter clinical testing The p.M4I variant (also known as c.12G>A), located in coding exon 1 of the BRIP1 gene, results from a G to A substitution at nucleotide position 12. The methionine at codon 4 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is poorly 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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