Submissions for variant NM_153240.5(NPHP3):c.1189C>T (p.Arg397Cys) (rs141477666)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000153593	SCV000203133	likely benign	not specified	2015-09-02	criteria provided, single submitter	clinical testing
Invitae	RCV000168169	SCV000218831	benign	Nephronophthisis	2019-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000153593	SCV000566586	uncertain significance	not specified	2017-06-27	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the NPHP3 gene. The R397C variant has been reported previously in two siblings with nephronophthisis; however, a second NPHP3 variant was not identified, and these siblings also had a homozygous deletion in NPHP1 (Hoefele et al., 2007). The R397C variant has also been identified in another individual with nephronophthisis who did not have a second NPHP3 variant identified (Halbritter et al., 2012). A different missense variant at the same position (R397H) has been reported in an individual with nephronophthisis and tapeto-retinal degeneration who did not have a second NPHP3 variant identified (Olbrich et al., 2003). The R379C variant is observed in 42/6614 (0.6%) alleles from individuals of non-Finnish European background, including 1 homozygous individual (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R397C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter 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.
Illumina Clinical Services Laboratory,Illumina	RCV001145350	SCV001306019	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	RCV001145351	SCV001306020	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.
Illumina Clinical Services Laboratory,Illumina	RCV001149669	SCV001310647	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.