ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.143C>A (p.Thr48Lys)

gnomAD frequency: 0.00001  dbSNP: rs755317452
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216242 SCV000279641 uncertain significance not provided 2023-04-17 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26315354, 11301010)
Color Diagnostics, LLC DBA Color Health RCV000584278 SCV000689261 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000698138 SCV000826781 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 48 of the BRIP1 protein (p.Thr48Lys). This variant is present in population databases (rs755317452, 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: 234642). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 RCV000584278 SCV001171921 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-14 criteria provided, single submitter clinical testing The p.T48K variant (also known as c.143C>A), located in coding exon 2 of the BRIP1 gene, results from a C to A substitution at nucleotide position 143. The threonine at codon 48 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.