ClinVar Miner

Submissions for variant NM_001379286.1(ZNF423):c.2621C>T (p.Pro874Leu)

gnomAD frequency: 0.00001  dbSNP: rs959264947
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001229648 SCV001402101 uncertain significance Nephronophthisis 14 2019-10-31 criteria provided, single submitter clinical testing 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ZNF423-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 866 of the ZNF423 protein (p.Pro866Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003490143 SCV004240856 uncertain significance not specified 2023-12-11 criteria provided, single submitter clinical testing Variant summary: ZNF423 c.2597C>T (p.Pro866Leu) results in a non-conservative amino acid change located in the Zinc finger C2H2-type domain (IPR013087) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251242 control chromosomes (gnomAD). 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.2597C>T in individuals affected with ZNF423-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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