ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3770C>T (p.Thr1257Ile)

gnomAD frequency: 0.00009  dbSNP: rs746967083
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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) RCV000728286 SCV000855839 uncertain significance not provided 2017-07-19 criteria provided, single submitter clinical testing
Invitae RCV001868929 SCV002170573 uncertain significance Nephronophthisis 2022-09-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1257 of the NPHP4 protein (p.Thr1257Ile). This variant is present in population databases (rs746967083, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NPHP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 593289). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
Fulgent Genetics, Fulgent Genetics RCV002485857 SCV002783060 uncertain significance Nephronophthisis 4; Senior-Loken syndrome 4 2021-12-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002535065 SCV003712802 uncertain significance Inborn genetic diseases 2022-12-27 criteria provided, single submitter clinical testing The c.3770C>T (p.T1257I) alteration is located in exon 27 (coding exon 26) of the NPHP4 gene. This alteration results from a C to T substitution at nucleotide position 3770, causing the threonine (T) at amino acid position 1257 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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