Submissions for variant NM_001278716.2(FBXL4):c.300T>C (p.Tyr100=)

gnomAD frequency: 0.00009  dbSNP: rs573472397

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000502389	SCV000598258	uncertain significance	Mitochondrial DNA depletion syndrome 13	2017-08-10	criteria provided, single submitter	reference population	The NM_012160.4:c.300T>C (NP_036292.2:p.Tyr100=) [GRCH38: NC_000006.12:g.98926689A>G] variant in FBXL4 gene is interpretated to be a Uncertain Significance - Conflicting Evidence based on ACMG guidelines (PMID: 25741868). This variant meets one or more of the following evidence codes reported in the ACMG-guideline. PM2:This variant is absent in key population databases. BP4:Computational evidence/predictors indicate no impact on the FBXL4 structure, function, or protein-protein interaction. BP7:The variant is silent with non predicted splice impact. Based on this evidence code ClinGen Pathogenicity Calculator (PMID:28081714) suggested that the variant is Uncertain Significance - Conflicting Evidence.
Invitae	RCV002524360	SCV003449543	likely benign	not provided	2023-12-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003900057	SCV004715602	likely benign	FBXL4-related condition	2023-07-25	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).