ClinVar Miner

Submissions for variant NM_001379286.1(ZNF423):c.290G>A (p.Arg97His)

gnomAD frequency: 0.00003  dbSNP: rs745597535
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000454256 SCV000538008 likely pathogenic Abnormal brain morphology criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001865411 SCV002225757 uncertain significance Nephronophthisis 14 2021-11-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 89 of the ZNF423 protein (p.Arg89His). This variant is present in population databases (rs745597535, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of Joubert syndrome (PMID: 26539891). ClinVar contains an entry for this variant (Variation ID: 402222). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect ZNF423 function (PMID: 32925911). 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.

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