ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.299-8T>A (rs73196229)

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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 RCV000079084 SCV000110953 benign not specified 2018-05-30 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000079084 SCV000304702 benign not specified 2016-02-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000283614 SCV000482293 benign Ornithine carbamoyltransferase deficiency 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000283614 SCV001156915 benign Ornithine carbamoyltransferase deficiency 2018-08-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000079084 SCV001364021 benign not specified 2019-03-14 criteria provided, single submitter clinical testing Variant summary: OTC c.299-8T>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.15 in 181703 control chromosomes in the gnomAD database, including 1881 homozygotes and 9206 hemizygotes. The observed variant frequency is approximately 33 fold of the estimated maximal expected allele frequency for a pathogenic variant in OTC causing Ornithine Transcarbamylase Deficiency phenotype (0.0046), strongly suggesting that the variant is benign. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

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