ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.3433T>C (p.Cys1145Arg)

gnomAD frequency: 0.00001  dbSNP: rs200287294
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001925436 SCV002168234 uncertain significance Nephronophthisis 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1145 of the NPHP3 protein (p.Cys1145Arg). This variant is present in population databases (rs200287294, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with NPHP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1403726). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NPHP3 protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002507007 SCV002815979 uncertain significance Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2022-02-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004538601 SCV004116261 uncertain significance NPHP3-related disorder 2023-01-30 criteria provided, single submitter clinical testing The NPHP3 c.3433T>C variant is predicted to result in the amino acid substitution p.Cys1145Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.043% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-132403535-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004042592 SCV004990972 uncertain significance Inborn genetic diseases 2023-12-22 criteria provided, single submitter clinical testing The c.3433T>C (p.C1145R) alteration is located in exon 24 (coding exon 24) of the NPHP3 gene. This alteration results from a T to C substitution at nucleotide position 3433, causing the cysteine (C) at amino acid position 1145 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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