Submissions for variant NM_018006.5(TRMU):c.652-2A>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003332050	SCV004039003	likely pathogenic	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2023-08-10	criteria provided, single submitter	clinical testing	Variant summary: TRMU c.652-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251414 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.652-2A>G in individuals affected with Liver Failure Acute Infantile, Transient and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV003475564	SCV004204363	likely pathogenic	Aminoglycoside-induced deafness	2023-08-24	criteria provided, single submitter	clinical testing