Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023386 | SCV001185254 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-02 | criteria provided, single submitter | clinical testing | The p.C167S variant (also known as c.499T>A), located in coding exon 5 of the NBN gene, results from a T to A substitution at nucleotide position 499. The cysteine at codon 167 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly 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. |
| Invitae | RCV001873370 | SCV002113255 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with serine at codon 167 of the NBN protein (p.Cys167Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). 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: 825352). 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 tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |