ClinVar Miner

Submissions for variant NM_004646.3(NPHS1):c.1638T>G (p.Thr546=) (rs115444936)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000366917 SCV000411572 uncertain significance Congenital nephrotic syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588114 SCV000698498 likely benign not provided 2016-10-17 criteria provided, single submitter clinical testing Variant summary: The NPHS1 c.1638T>G (p.Thr546Thr) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC with an allele frequency of 195/119054 (1/610 including 2 homozygotes), predominantly observed in the European (Non-Finnish) cohort, 166/65658 (1/395, 1 homozygote), which does not exceed the estimated maximal expected allele frequency for a pathogenic NPHS1 variant of 1/298. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as "Likely Benign."
Athena Diagnostics Inc RCV000588114 SCV000842913 benign not provided 2018-01-15 criteria provided, single submitter clinical testing
Invitae RCV000588114 SCV001096571 benign not provided 2020-12-06 criteria provided, single submitter clinical testing
Natera, Inc. RCV001277291 SCV001464213 likely benign Finnish congenital nephrotic syndrome 2019-11-11 no assertion criteria provided clinical testing

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