ClinVar Miner

Submissions for variant NM_001367624.2(ZNF469):c.10420C>T (p.Arg3474Trp)

gnomAD frequency: 0.00003  dbSNP: rs1394199246
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001333790 SCV001526470 uncertain significance Brittle cornea syndrome 1 2018-05-15 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002395735 SCV002702352 uncertain significance Cardiovascular phenotype 2021-08-10 criteria provided, single submitter clinical testing The p.R3446W variant (also known as c.10336C>T), located in coding exon 2 of the ZNF469 gene, results from a C to T substitution at nucleotide position 10336. The arginine at codon 3446 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002546651 SCV003483524 uncertain significance not provided 2022-05-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 3446 of the ZNF469 protein (p.Arg3446Trp). This variant is present in population databases (no rsID available, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. ClinVar contains an entry for this variant (Variation ID: 1031848). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
PreventionGenetics, part of Exact Sciences RCV003399115 SCV004118919 uncertain significance ZNF469-related disorder 2022-12-16 criteria provided, single submitter clinical testing The ZNF469 c.10336C>T variant is predicted to result in the amino acid substitution p.Arg3446Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-88504298-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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