ClinVar Miner

Submissions for variant NM_153240.5(NPHP3):c.2080A>G (p.Lys694Glu)

gnomAD frequency: 0.00003  dbSNP: rs374742856
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000593072 SCV000704759 uncertain significance not provided 2016-12-19 criteria provided, single submitter clinical testing
Invitae RCV001854038 SCV002195922 uncertain significance Nephronophthisis 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 694 of the NPHP3 protein (p.Lys694Glu). This variant is present in population databases (rs374742856, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NPHP3-related conditions. ClinVar contains an entry for this variant (Variation ID: 499325). 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 NPHP3 protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV002476303 SCV002791363 uncertain significance Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome 2022-01-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002531043 SCV003672806 uncertain significance Inborn genetic diseases 2022-12-19 criteria provided, single submitter clinical testing The c.2080A>G (p.K694E) alteration is located in exon 14 (coding exon 14) of the NPHP3 gene. This alteration results from a A to G substitution at nucleotide position 2080, causing the lysine (K) at amino acid position 694 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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