Submissions for variant NM_000254.3(MTR):c.3007+1G>A

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	RCV004800063	SCV005423388	likely pathogenic	Methylcobalamin deficiency type cblG	2024-10-04	criteria provided, single submitter	clinical testing	Variant summary: MTR c.3007+1G>A 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of MTR function. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. One predict the variant abolishes a cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.3007+1G>A in individuals affected with Methylcobalamin deficiency type cblG and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.