ClinVar Miner

Submissions for variant NM_001379286.1(ZNF423):c.2006A>C (p.Lys669Thr)

gnomAD frequency: 0.00049  dbSNP: rs145272522
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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 RCV001065901 SCV001230891 uncertain significance Nephronophthisis 14 2022-10-04 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 661 of the ZNF423 protein (p.Lys661Thr). This variant is present in population databases (rs145272522, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. 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: 859727). 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.
Ambry Genetics RCV004030592 SCV003710222 uncertain significance not specified 2021-08-02 criteria provided, single submitter clinical testing The c.1982A>C (p.K661T) alteration is located in exon 5 (coding exon 4) of the ZNF423 gene. This alteration results from a A to C substitution at nucleotide position 1982, causing the lysine (K) at amino acid position 661 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003938429 SCV004752733 likely benign ZNF423-related disorder 2023-12-18 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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