Submissions for variant NM_153240.5(NPHP3):c.1813C>T (p.Arg605Cys)

gnomAD frequency: 0.00014  dbSNP: rs144731534

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000355084	SCV000441121	uncertain significance	Meckel-Gruber syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000260312	SCV000441122	uncertain significance	Renal-hepatic-pancreatic dysplasia 1	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000301526	SCV000441123	uncertain significance	Nephronophthisis	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000301526	SCV001378892	uncertain significance	Nephronophthisis	2022-10-25	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 605 of the NPHP3 protein (p.Arg605Cys). This variant is present in population databases (rs144731534, gnomAD 0.03%). 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: 343387). 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) performed at Invitae indicates that this missense variant is not expected to disrupt NPHP3 protein function. 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.
GeneDx	RCV002288977	SCV002578598	uncertain significance	not provided	2022-04-05	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002487508	SCV002775093	uncertain significance	Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome	2022-05-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002520083	SCV003741085	uncertain significance	Inborn genetic diseases	2022-09-07	criteria provided, single submitter	clinical testing	The c.1813C>T (p.R605C) alteration is located in exon 12 (coding exon 12) of the NPHP3 gene. This alteration results from a C to T substitution at nucleotide position 1813, causing the arginine (R) at amino acid position 605 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004530388	SCV004747754	uncertain significance	NPHP3-related disorder	2023-12-23	no assertion criteria provided	clinical testing	The NPHP3 c.1813C>T variant is predicted to result in the amino acid substitution p.Arg605Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.