Submissions for variant NM_001367624.2(ZNF469):c.3119A>C (p.Lys1040Thr)

gnomAD frequency: 0.00002  dbSNP: rs273585619

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001824605	SCV002074337	uncertain significance	not specified	2024-05-30	criteria provided, single submitter	clinical testing	Variant summary: ZNF469 c.3119A>C (p.Lys1040Thr) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 99330 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3119A>C has been reported in the literature as a heterozygous variant in an individual affected with Keratoconus (example, Lechner_2014). This report does not provide unequivocal conclusions about association of the variant with Brittle Cornea Syndrome 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 24895405). ClinVar contains an entry for this variant (Variation ID: 126924). Based on the evidence outlined above, the variant was classified as uncertain significance.
Willoughby Group, Queen's University Belfast	RCV000114780	SCV000148675	pathogenic	Keratoconus 1		no assertion criteria provided	not provided	Converted during submission to Pathogenic.