Submissions for variant NM_001379286.1(ZNF423):c.1274G>A (p.Arg425Gln)

gnomAD frequency: 0.00001  dbSNP: rs150550744

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000798968	SCV000938613	uncertain significance	Nephronophthisis 14	2018-12-05	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 417 of the ZNF423 protein (p.Arg417Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs150550744, ExAC 0.005%). This variant has not been reported in the literature in individuals with ZNF423-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003411757	SCV004139296	uncertain significance	not provided	2023-05-01	criteria provided, single submitter	clinical testing