ClinVar Miner

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

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Total submissions: 6
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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.

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