ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.1174C>T (p.Arg392Ter)

gnomAD frequency: 0.00001  dbSNP: rs1485445500
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000785914 SCV000924490 pathogenic Nephronophthisis 3 2018-06-15 criteria provided, single submitter research The heterozygous p.Arg392Ter variant was identified by our study in the compound heterozygous state, with a pathogenic variant, in one individual with nephronophthisis. This variant has been identified in <0.01% (1/25790) of European (Finnish) chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs143197357). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Loss of function of the NPHP3 gene is an established disease mechanism in autosomal recessive nephronophthisis, and this is a loss of function variant. In summary, this variant is pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002507353 SCV002816560 pathogenic Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2022-01-08 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003133591 SCV003817438 likely pathogenic not provided 2021-12-28 criteria provided, single submitter clinical testing
Invitae RCV003748283 SCV004535219 pathogenic Nephronophthisis 2024-01-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg392*) 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 (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with juvenile nephronophthisis (PMID: 31131822). ClinVar contains an entry for this variant (Variation ID: 635041). 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.

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