ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3127A>G (p.Asn1043Asp)

dbSNP: rs587782630
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132015 SCV000187074 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-21 criteria provided, single submitter clinical testing The p.N1043D variant (also known as c.3127A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3127. The asparagine at codon 1043 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available higher primate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001342041 SCV001535943 uncertain significance Hereditary breast ovarian cancer syndrome 2023-04-11 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 142668). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1043 of the BRCA1 protein (p.Asn1043Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. 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 BRCA1 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000132015 SCV003847548 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998282 SCV005626066 uncertain significance not provided 2024-11-29 criteria provided, single submitter clinical testing The BRCA1 c.3127A>G (p.Asn1043Asp) variant has been reported to be located in a region of the BRCA1 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). To the best of our knowledge, this variant has not been reported in individuals with BRCA1-related disorders. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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