ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.2951C>T (p.Thr984Met)

gnomAD frequency: 0.00009  dbSNP: rs377729557
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001060572 SCV001225271 uncertain significance Nephronophthisis 2022-09-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 984 of the NPHP4 protein (p.Thr984Met). This variant is present in population databases (rs377729557, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of Senior–Løken syndrome (PMID: 32865313). ClinVar contains an entry for this variant (Variation ID: 855326). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NPHP4 protein function. 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 RCV001570328 SCV001794606 uncertain significance not provided 2022-11-05 criteria provided, single submitter clinical testing Identified in a patient with a clinical diagnosis of Senior-Loken syndrome, in cis with another missense allele (Sallum et al., 2020); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32865313)
Fulgent Genetics, Fulgent Genetics RCV002497442 SCV002781021 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2021-10-25 criteria provided, single submitter clinical testing

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