ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.1076A>G (p.Asn359Ser)

gnomAD frequency: 0.00001  dbSNP: rs768886664
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000796652 SCV000936173 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 359 of the NBN protein (p.Asn359Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs768886664, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 492073). 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: "Possibly Damaging"; Align-GVGD: "Class C15"). 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 RCV000583638 SCV001169975 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-08 criteria provided, single submitter clinical testing The p.N359S variant (also known as c.1076A>G), located in coding exon 9 of the NBN gene, results from an A to G substitution at nucleotide position 1076. The asparagine at codon 359 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly 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.
GeneDx RCV001764710 SCV001989880 uncertain significance not provided 2019-05-16 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Genome-Nilou Lab RCV000796652 SCV002044711 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing

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