Submissions for variant NM_024996.7(GFM1):c.689+887G>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	RCV005238515	SCV005886560	uncertain significance	not specified	2025-02-05	criteria provided, single submitter	clinical testing	Variant summary: GFM1 c.689+887G>A (also known as c.729G>A, p.Trp243X in NM_001308164) is located at a position not widely known to affect splicing. Consensus agreement among computation 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 5.2e-05 in 134628 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.689+887G>A has been reported in the literature in one WES case with unknown phenotype (Cohen_2024). The report does not provide unequivocal conclusions about association of the variant with Combined Oxidative Phosphorylation Deficiency 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 38523675). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance.