ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1670C>T (p.Ser557Phe)

gnomAD frequency: 0.00001  dbSNP: rs1375911072
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001199256 SCV001370319 uncertain significance Fanconi anemia complementation group J 2019-05-13 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: BP1.
Labcorp Genetics (formerly Invitae), Labcorp RCV001321609 SCV001512446 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2024-12-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 557 of the BRIP1 protein (p.Ser557Phe). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 932097). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRIP1 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.
Ambry Genetics RCV002402564 SCV002708509 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-29 criteria provided, single submitter clinical testing The p.S557F variant (also known as c.1670C>T), located in coding exon 11 of the BRIP1 gene, results from a C to T substitution at nucleotide position 1670. The serine at codon 557 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is not well 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.
GeneDx RCV002473215 SCV002770357 uncertain significance not provided 2022-06-20 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 RCV003462670 SCV004217063 uncertain significance Familial cancer of breast 2023-07-08 criteria provided, single submitter clinical testing

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