Submissions for variant NM_015909.4(NBAS):c.2764-1G>C

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002302548	SCV002598904	likely pathogenic	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2022-09-17	criteria provided, single submitter	clinical testing	Variant summary: NBAS c.2764-1G>C 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 canonical 3' acceptor site and two predict the variant creates a 3' acceptor site located 9 nucleotides downstream of the canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251236 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2764-1G>C in individuals affected with Liver Failure Acute Infantile, Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.