ClinVar Miner

Submissions for variant NM_001379286.1(ZNF423):c.3301G>A (p.Ala1101Thr)

gnomAD frequency: 0.00006  dbSNP: rs144425413
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489203 SCV000577312 uncertain significance not provided 2017-04-04 criteria provided, single submitter clinical testing The A1093T variant in the ZNF423 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A1093T variant is observed in 5/5739 (0.009%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The A1093T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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 A1093T as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001316620 SCV001507251 uncertain significance Nephronophthisis 14 2022-06-20 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1093 of the ZNF423 protein (p.Ala1093Thr). This variant is present in population databases (rs144425413, gnomAD 0.007%). 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: 426779). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004701544 SCV005203016 uncertain significance not specified 2024-07-22 criteria provided, single submitter clinical testing Variant summary: ZNF423 c.3277G>A (p.Ala1093Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 213550 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3277G>A in individuals affected with ZNF423-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 426779). Based on the evidence outlined above, the variant was classified as uncertain significance.

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