Submissions for variant NM_153240.5(NPHP3):c.233G>T (p.Gly78Val)

gnomAD frequency: 0.00006  dbSNP: rs202142404

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726607	SCV000345803	uncertain significance	not provided	2016-09-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000283485	SCV000441157	uncertain significance	Nephronophthisis	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000343202	SCV000441158	uncertain significance	Renal-hepatic-pancreatic dysplasia 1	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000404760	SCV000441159	uncertain significance	Meckel-Gruber syndrome	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000726607	SCV000590321	uncertain significance	not provided	2017-06-13	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NPHP3 gene. The G78V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G78V variant is observed in 1/8252 (0.01%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G78V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000283485	SCV000831174	uncertain significance	Nephronophthisis	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 78 of the NPHP3 protein (p.Gly78Val). This variant is present in population databases (rs202142404, gnomAD 0.01%). 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: 291105). 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.
Fulgent Genetics, Fulgent Genetics	RCV002502158	SCV002812076	uncertain significance	Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome	2022-05-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021321	SCV004990282	uncertain significance	Inborn genetic diseases	2023-12-22	criteria provided, single submitter	clinical testing	The c.233G>T (p.G78V) alteration is located in exon 1 (coding exon 1) of the NPHP3 gene. This alteration results from a G to T substitution at nucleotide position 233, causing the glycine (G) at amino acid position 78 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.