ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.189_192del (p.Phe63fs)

dbSNP: rs1553200990
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000595534 SCV000708173 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193268 SCV001361999 likely pathogenic Nephronophthisis 4 2019-03-05 criteria provided, single submitter clinical testing Variant summary: NPHP4 c.189_192delTGAT (p.Phe63LeufsX16) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in several individuals affected with Nephronophthisis 4 in HGMD. The variant allele was found at a frequency of 4.2e-06 in 238746 control chromosomes (gnomAD). To our knowledge, no occurrence of c.189_192delTGAT in individuals affected with Nephronophthisis 4, and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV003117367 SCV003789288 pathogenic Nephronophthisis 2022-07-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 501697). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Phe63Leufs*16) in the NPHP4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPHP4 are known to be pathogenic (PMID: 12205563, 23559409).

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