ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.958-2A>G

gnomAD frequency: 0.00006  dbSNP: rs780148543
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001052653 SCV001216874 pathogenic Nephronophthisis 2023-07-14 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the NPHP3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NPHP3 are known to be pathogenic (PMID: 18371931, 23559409). This variant is present in population databases (rs780148543, gnomAD 0.008%). Disruption of this splice site has been observed in individual(s) with clinical features of nephronophthisis (PMID: 24776604). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 848816). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001797150 SCV002039043 pathogenic not provided 2023-07-18 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24776604, 31964843, 36090483)
Fulgent Genetics, Fulgent Genetics RCV002505602 SCV002810883 pathogenic Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2022-04-07 criteria provided, single submitter clinical testing

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