Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2_SupportingPP5BP4
The NM_005957(MTHFR):c.1969T>C(p.Ter657ArgextTer50) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152184 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. *657*) has been classified as Likely benign.
Verdict is Uncertain_significance. Variant got 1 ACMG points.
GnomAD3 genomes AF: 0.00000657AC: 1AN: 152184Hom.: 0Cov.: 33 GnomAD3 exomes AF: 0.00000398AC: 1AN: 251226Hom.: 0 AF XY: 0.00AC XY: 0AN XY: 135786 GnomAD4 exome AF: 0.00000159AC: 1AN: 628700Hom.: 0 AF XY: 0.00000292AC XY: 1AN XY: 342478
Submissions by phenotype
Homocystinuria due to methylene tetrahydrofolate reductase deficiency
|Pathogenic, no assertion criteria provided||clinical testing||University Children's Hospital, University of Zurich||-||- -|
Find out detailed SpliceAI scores and Pangolin per-transcript scores at