Submissions for variant NM_001367624.2(ZNF469):c.10330G>C (p.Gly3444Arg)

gnomAD frequency: 0.00135  dbSNP: rs569602115

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000320795	SCV000399443	uncertain significance	Brittle cornea syndrome 1	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000488947	SCV000577506	uncertain significance	not specified	2017-03-27	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the ZNF469 gene. The G3416R variant has not been published as pathogenic or been reported as benign to our knowledge. The G3416R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Additionally, G3416R has been observed in 2/166 (1.2%) alleles from individuals of Latino ancestry and in 2/596 (0.3%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015).
Fulgent Genetics, Fulgent Genetics	RCV000320795	SCV000896571	uncertain significance	Brittle cornea syndrome 1	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV002056535	SCV002341659	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002379207	SCV002694406	benign	Cardiovascular phenotype	2023-04-13	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003957656	SCV004769091	likely benign	ZNF469-related disorder	2024-02-20	criteria provided, single submitter	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).