ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.133C>T (p.Gln45Ter) (rs370210428)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000681812 SCV000890172 pathogenic not provided 2018-07-30 criteria provided, single submitter clinical testing The Q45X variant in the NPHP4 gene has been reported previously in the heterozygous state in an individual with nephronophthisis-related ciliopathy who had end-stage renal disease and no extra-renal manifestations (Halbritter et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q45X variant is observed in 9/126,618 alleles (0.0071%) from individuals of non-Finnish European background, and 9/277,008 global alleles (0.0032%) in large population cohorts (Lek et al., 2016). We interpret Q45X as a pathogenic variant.
Invitae RCV001237139 SCV001409890 pathogenic Nephronophthisis 2019-11-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln45*) in the NPHP4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs370210428, ExAC 0.008%). This variant has been observed in an individual affected with a nephronophthisis-related ciliopathy (PMID: 23559409). ClinVar contains an entry for this variant (Variation ID: 562355). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in NPHP4 are known to be pathogenic (PMID: 12205563, 23559409). For these reasons, this variant has been classified as Pathogenic.
Gharavi Laboratory,Columbia University RCV000681812 SCV000809283 pathogenic not provided 2018-09-16 no assertion criteria provided research

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