Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521326 | SCV000618799 | uncertain significance | not provided | 2017-07-14 | criteria provided, single submitter | clinical testing | The A893V variant in the ZNF423 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A893V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A893V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A893V as a variant of uncertain significance. |
| Labcorp Genetics |
RCV001062559 | SCV001227368 | uncertain significance | Nephronophthisis 14 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with valine at codon 893 of the ZNF423 protein (p.Ala893Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ZNF423-related conditions. ClinVar contains an entry for this variant (Variation ID: 450244). 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. 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. |