ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.2563C>T (p.Gln855Ter)

gnomAD frequency: 0.00002  dbSNP: rs201237799
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000692736 SCV000820576 pathogenic Nephronophthisis 2023-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln855*) 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). This variant is present in population databases (rs201237799, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with infantile nephronophthisis (PMID: 19177160). ClinVar contains an entry for this variant (Variation ID: 571559). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001561432 SCV001784038 likely pathogenic not provided 2023-06-28 criteria provided, single submitter clinical testing Identified in an individual with nephronophthisis who also harbored a second variant in NPHP3 (Tory et al., 2009); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 31980526, 36090483, 31345219, 19177160)
Fulgent Genetics, Fulgent Genetics RCV002485656 SCV002793886 likely pathogenic Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2022-04-08 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV003485630 SCV004239066 pathogenic NPHP3-related Meckel-like syndrome 2023-10-06 criteria provided, single submitter clinical testing NPHP3 c.2563C>T has been reported in the compound heterozygous state in at least one patient with nephronophthisis, and has also been reported in ClinVar (Variation ID 571559). This variant (rs201237799) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 11/282752 total alleles; 0.004%; no homozygotes). This nonsense variant results in a premature stop codon in exon 18 of 27, likely leading to nonsense-mediated decay and lack of protein production. We consider c.2563C>T in NPHP3 to be pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.