ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3272del (p.Val1091fs)

gnomAD frequency: 0.00002  dbSNP: rs1278089386
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002460878 SCV002757620 pathogenic not provided 2022-05-25 criteria provided, single submitter clinical testing Frameshift 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; Identified in the heterozygous state using alternate nomenclature c.2477delT in a family with Cogan syndrome and nephronophthisis, however, a second variant was not identified (Mollet et al, 2002); This variant is associated with the following publications: (PMID: 31589614, 21866095, 12244321)
Fulgent Genetics, Fulgent Genetics RCV002490303 SCV002775953 pathogenic Nephronophthisis 4; Senior-Loken syndrome 4 2022-05-18 criteria provided, single submitter clinical testing
Invitae RCV002512712 SCV003485735 pathogenic Nephronophthisis 2022-12-05 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 3403). This premature translational stop signal has been observed in individual(s) with Senior-Loken syndrome (PMID: 21866095). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Val1091Glyfs*31) 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). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003415637 SCV004118505 pathogenic NPHP4-related condition 2023-06-22 criteria provided, single submitter clinical testing The NPHP4 c.3272delT variant is predicted to result in a frameshift and premature protein termination (p.Val1091Glyfs*31). This variant has been reported in the homozygous state or heterozygous with another variant in multiple individuals with nephronophthisis or end-stage renal disease (reported as 2744delT in Table 1 and Figure 1, Mollet et al. 2002. PubMed ID: 12244321; Table 1, Otto et al. 2002. PubMed ID: 12205563; Table 2, Halbritter et al. 2013. PubMed ID: 23559409). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-5933354-CA-C). Frameshift variants in NPHP4 are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM RCV000003572 SCV000023730 pathogenic Nephronophthisis 4 2002-10-01 no assertion criteria provided literature only

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