ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.2222G>A (p.Cys741Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1451958461
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001202287 SCV001373395 uncertain significance Nephronophthisis 2019-10-01 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 741 of the NPHP3 protein (p.Cys741Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. 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. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NPHP3-related conditions. This variant is not present in population databases (ExAC no frequency).
Fulgent Genetics, Fulgent Genetics RCV002491603 SCV002791714 uncertain significance Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2022-05-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002561094 SCV003630535 uncertain significance Inborn genetic diseases 2022-06-09 criteria provided, single submitter clinical testing The c.2222G>A (p.C741Y) alteration is located in exon 16 (coding exon 16) of the NPHP3 gene. This alteration results from a G to A substitution at nucleotide position 2222, causing the cysteine (C) at amino acid position 741 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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