ClinVar Miner

Submissions for variant NM_001379286.1(ZNF423):c.296C>T (p.Pro99Leu)

gnomAD frequency: 0.00002  dbSNP: rs553868296
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001238251 SCV001411051 uncertain significance Nephronophthisis 14 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 91 of the ZNF423 protein (p.Pro91Leu). This variant is present in population databases (rs553868296, gnomAD 0.006%). 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: 964101). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ZNF423 protein function. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV001238251 SCV005042556 uncertain significance Nephronophthisis 14 criteria provided, single submitter clinical testing The missense variant c.296C>Tp.Pro99Leu in ZNF423 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is reported with 0.003% allele frequency in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance.The amino acid Proline at position 99 is changed to a Leucine changing protein sequence and it might alter its composition and physico-chemical properties.The amino acid change p.Arg406Trp in ZNF423 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Breakthrough Genomics, Breakthrough Genomics RCV004692279 SCV005194369 uncertain significance not provided criteria provided, single submitter not provided

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