Submissions for variant NM_153240.5(NPHP3):c.233G>T (p.Gly78Val) (rs202142404)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000726607	SCV000345803	uncertain significance	not provided	2016-09-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000283485	SCV000441157	uncertain significance	Nephronophthisis	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000343202	SCV000441158	uncertain significance	Renal-hepatic-pancreatic dysplasia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,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	2018-12-21	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with valine at codon 78 of the NPHP3 protein (p.Gly78Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs202142404, ExAC 0.01%). This variant has not been reported in the literature in individuals with NPHP3-related disease. ClinVar contains an entry for this variant (Variation ID: 291105). 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: "Benign"; 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.