Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001886941 | SCV002161549 | uncertain significance | not provided | 2021-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 2979 of the ZNF469 protein (p.Asp2979Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. 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 asparagine 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. |
| Revvity Omics, |
RCV003136259 | SCV003821849 | uncertain significance | Brittle cornea syndrome 1 | 2024-01-18 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003166956 | SCV003912757 | uncertain significance | Cardiovascular phenotype | 2023-02-05 | criteria provided, single submitter | clinical testing | The p.D2979N variant (also known as c.8935G>A), located in coding exon 2 of the ZNF469 gene, results from a G to A substitution at nucleotide position 8935. The aspartic acid at codon 2979 is replaced by asparagine, an amino acid with highly similar 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. |
| Mayo Clinic Laboratories, |
RCV001886941 | SCV004227628 | uncertain significance | not provided | 2023-05-05 | criteria provided, single submitter | clinical testing | BP4 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004526876 | SCV005039631 | uncertain significance | not specified | 2024-03-21 | criteria provided, single submitter | clinical testing | Variant summary: ZNF469 c.9019G>A (p.Asp3007Asn) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 149204 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.9019G>A in individuals affected with Brittle Cornea Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1388989). Based on the evidence outlined above, the variant was classified as uncertain significance. |