ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.1985+5G>A

dbSNP: rs754508002
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001212619 SCV001384208 uncertain significance Nephronophthisis 2022-08-23 criteria provided, single submitter clinical testing This sequence change falls in intron 13 of the NPHP3 gene. It does not directly change the encoded amino acid sequence of the NPHP3 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs754508002, gnomAD 0.003%). This variant has been observed in individual(s) with clinical features of NPHP3-related conditions (PMID: 18371931). ClinVar contains an entry for this variant (Variation ID: 2639). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 13 and introduces a premature termination codon (PMID: 18371931). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV003221779 SCV003918318 likely pathogenic not provided 2022-10-14 criteria provided, single submitter clinical testing Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and published functional studies demonstrate skipping of exon 13 and an out-of-frame transcript that results in protein truncation (Bergmann et al., 2008); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18371931, 21845392)
Revvity Omics, Revvity RCV003221779 SCV004235624 uncertain significance not provided 2023-11-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005024994 SCV005658920 likely pathogenic Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2024-05-15 criteria provided, single submitter clinical testing
OMIM RCV000002758 SCV000022916 pathogenic Renal-hepatic-pancreatic dysplasia 1 2008-04-01 no assertion criteria provided literature only

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