Submissions for variant NM_153240.5(NPHP3):c.3499C>T (p.Arg1167Cys)

gnomAD frequency: 0.00001  dbSNP: rs201135796

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000704419	SCV000833368	uncertain significance	Nephronophthisis	2022-09-07	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1167 of the NPHP3 protein (p.Arg1167Cys). This variant is present in population databases (rs201135796, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with NPHP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 580774). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Eurofins Ntd Llc (ga)	RCV000732403	SCV000860360	uncertain significance	not provided	2018-03-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000732403	SCV002001989	uncertain significance	not provided	2020-02-10	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002493237	SCV002791445	uncertain significance	Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome	2022-03-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004958042	SCV005464507	uncertain significance	Inborn genetic diseases	2024-12-10	criteria provided, single submitter	clinical testing	The c.3499C>T (p.R1167C) alteration is located in exon 24 (coding exon 24) of the NPHP3 gene. This alteration results from a C to T substitution at nucleotide position 3499, causing the arginine (R) at amino acid position 1167 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genomics Laboratory, Stanford Medicine	RCV005253085	SCV005903534	uncertain significance	Familial aplasia of the vermis; Meckel-Gruber syndrome; Renal-hepatic-pancreatic dysplasia 1; Renal dysplasia and retinal aplasia; Nephronophthisis	2022-09-09	criteria provided, single submitter	clinical testing
Clinical Genomics Laboratory, Stanford Medicine	RCV005256672	SCV005911289	uncertain significance	Familial aplasia of the vermis; Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome; Renal dysplasia and retinal aplasia	2022-09-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004535749	SCV004115954	uncertain significance	NPHP3-related disorder	2024-07-22	no assertion criteria provided	clinical testing	The NPHP3 c.3499C>T variant is predicted to result in the amino acid substitution p.Arg1167Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.