Submissions for variant NM_153240.5(NPHP3):c.3281G>A (p.Arg1094Gln) (rs146890274)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000724039	SCV000228091	uncertain significance	not provided	2017-10-05	criteria provided, single submitter	clinical testing
Genetic Services Laboratory,University of Chicago	RCV000194551	SCV000248268	uncertain significance	not specified	2015-03-11	criteria provided, single submitter	clinical testing
Invitae	RCV001066929	SCV001231953	uncertain significance	Nephronophthisis	2019-12-30	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 1094 of the NPHP3 protein (p.Arg1094Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs146890274, ExAC 0.07%). This variant has not been reported in the literature in individuals with NPHP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 195784). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Illumina Clinical Services Laboratory,Illumina	RCV001147011	SCV001307778	uncertain significance	Nephronophthisis 3	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV001147012	SCV001307779	uncertain significance	Renal-hepatic-pancreatic dysplasia 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina	RCV001147013	SCV001307780	uncertain significance	Meckel syndrome type 7	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.