ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.469del (p.Arg157fs)

gnomAD frequency: 0.00002  dbSNP: rs773760404
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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 RCV001939549 SCV002233131 pathogenic Nephronophthisis 2021-10-31 criteria provided, single submitter clinical testing This variant is present in population databases (rs773760404, gnomAD 0.03%). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NPHP3-related conditions. This sequence change creates a premature translational stop signal (p.Arg157Glufs*31) in the NPHP3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHP3 are known to be pathogenic (PMID: 18371931, 23559409).
Fulgent Genetics, Fulgent Genetics RCV002497873 SCV002806398 likely pathogenic Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2024-05-13 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV003485752 SCV004239067 pathogenic NPHP3-related Meckel-like syndrome 2023-10-06 criteria provided, single submitter clinical testing This NPHP3 variant (rs773760404) is rare (<0.1%) in a large population dataset (gnomAD v3.1.2: 3/151942 total alleles; 0.002%; no homozygotes). It has been reported in ClinVar (Variation ID 1454636), but has not been reported in the literature, to our knowledge. This frameshift variant results in a premature stop codon in exon 3 of 27, likely leading to nonsense-mediated decay and lack of protein production. We consider c.469del in NPHP3 to be pathogenic.
PreventionGenetics, part of Exact Sciences RCV004741167 SCV005348113 likely pathogenic NPHP3-related disorder 2024-04-19 no assertion criteria provided clinical testing The NPHP3 c.469delA variant is predicted to result in a frameshift and premature protein termination (p.Arg157Glufs*31). This variant has been reported in a cohort study about retinal diseases (Hanany et al. 2020. PubMed ID: 31964843. Table S3). This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in NPHP3 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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