rs786204022
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_005957.5(MTHFR):c.1060C>T(p.His354Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H354H) has been classified as Likely benign.
Frequency
Consequence
NM_005957.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251248Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135880
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461590Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727052
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Homocystinuria due to methylene tetrahydrofolate reductase deficiency Pathogenic:1Uncertain:1
This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 354 of the MTHFR protein (p.His354Tyr). This variant is present in population databases (rs786204022, gnomAD 0.003%). This missense change has been observed in individual(s) with methylenetetrahydrofolate reductase deficiency (PMID: 25736335). This variant is also known as c.1072C>T. ClinVar contains an entry for this variant (Variation ID: 187888). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects MTHFR function (PMID: 27743313). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at