ClinVar Miner

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

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Total submissions: 3
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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 not provided 2019-02-27 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.

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