Submissions for variant NM_001379286.1(ZNF423):c.2762C>T (p.Pro921Leu)

gnomAD frequency: 0.00023  dbSNP: rs200585917

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000030826	SCV001208507	uncertain significance	Nephronophthisis 14	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 913 of the ZNF423 protein (p.Pro913Leu). This variant is present in population databases (rs200585917, gnomAD 0.03%). This missense change has been observed in individual(s) with nephronophthisis (PMID: 22863007). ClinVar contains an entry for this variant (Variation ID: 37287). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ZNF423 protein function. Experimental studies have shown that this missense change does not substantially affect ZNF423 function (PMID: 22863007, 32925911). 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.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000030826	SCV005438602	uncertain significance	Nephronophthisis 14	2024-12-18	criteria provided, single submitter	clinical testing
OMIM	RCV000030826	SCV000053501	pathogenic	Nephronophthisis 14	2012-08-03	no assertion criteria provided	literature only