ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.530T>C (p.Phe177Ser)

dbSNP: rs1064796090
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482441 SCV000572515 uncertain significance not provided 2016-12-21 criteria provided, single submitter clinical testing This variant is denoted NBN c.530T>C at the cDNA level, p.Phe177Ser (F177S) at the protein level, and results in the change of a Phenylalanine to a Serine (TTT>TCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NBN Phe177Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Phenylalanine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. NBN Phe177Ser occurs at a position that is conserved across species and is located in within the BRCT domain as well as the region that mediates interaction with SP100 (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether NBN Phe177Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001302493 SCV001491705 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-03-04 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 177 of the NBN protein (p.Phe177Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 422916). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Genome-Nilou Lab RCV001302493 SCV002045184 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing

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