ClinVar Miner

Submissions for variant NM_001367624.2(ZNF469):c.11185G>A (p.Gly3729Ser)

gnomAD frequency: 0.00009  dbSNP: rs273585629
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001854536 SCV002199214 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 3701 of the ZNF469 protein (p.Gly3701Ser). This variant is present in population databases (rs273585629, gnomAD 0.02%). This missense change has been observed in individual(s) with keratoconus (PMID: 24895405). ClinVar contains an entry for this variant (Variation ID: 126918). 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 serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 RCV002433602 SCV002745366 uncertain significance Cardiovascular phenotype 2022-11-04 criteria provided, single submitter clinical testing The p.G3701S variant (also known as c.11101G>A), located in coding exon 2 of the ZNF469 gene, results from a G to A substitution at nucleotide position 11101. The glycine at codon 3701 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. 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.
CeGaT Center for Human Genetics Tuebingen RCV001854536 SCV004702829 uncertain significance not provided 2024-01-01 criteria provided, single submitter clinical testing ZNF469: PM2, BP4
Willoughby Group, Queen's University Belfast RCV000114774 SCV000148669 pathogenic Keratoconus 1 no assertion criteria provided not provided Converted during submission to Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004751264 SCV005357853 uncertain significance ZNF469-related disorder 2024-08-06 no assertion criteria provided clinical testing The ZNF469 c.11101G>A variant is predicted to result in the amino acid substitution p.Gly3701Ser. This variant was reported in an individual with keratoconus (Lechner et al. 2014. PubMed ID: 24895405). This variant is reported in 0.019% of alleles in individuals of African descent in gnomAD. 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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