ClinVar Miner

Submissions for variant NM_015102.5(NPHP4):c.3329C>T (p.Ala1110Val) (rs139767853)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000081715 SCV000113646 likely benign not specified 2016-11-09 criteria provided, single submitter clinical testing
GeneDx RCV000081715 SCV000513952 uncertain significance not specified 2016-05-19 criteria provided, single submitter clinical testing The A1110V variant in the NPHP4 gene was reported in an individual with pulmonary atresia, ventricular septal defect, right lung isomerism, and abdominal situs inversus as well as in an individual with a complex cardiac laterality defect; however it is unknown whether these individuals carried another variant in the NPHP4 gene and the A1110V variant was also identified in two control chromosomes (French et al., 2012). A1110V is reported as a variant of uncertain significance in ClinVar by a different clinical laboratory, but additional evidence is not available (ClinVar SCV000113646.4; Landrum et al., 2015). The NHLBI ESP Exome Sequencing Project reports A1110V was observed in 57/8510 alleles (0.67%) from individuals of European American background; however, the A1110V variant was not present in the homozygous state in any individual within this population. The A1110V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species, with Valine being present in other mammals. In silico analysis predicts this variant likely does not alter the protein structure/function. As an alternate mechanism, plice predictor models show that A1110V creates a cryptic donor splice site upstream of the natural donor site of intron 24, which may result in abnormal gene splicing; however, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown. Therefore, we interpret A1110V as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000292444 SCV000358428 uncertain significance Nephronophthisis 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000331197 SCV000358429 uncertain significance Renal dysplasia and retinal aplasia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000292444 SCV000556431 benign Nephronophthisis 2017-07-11 criteria provided, single submitter clinical testing

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