rs200137991
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate
The NM_005957.5(MTHFR):c.1262G>T(p.Trp421Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W421C) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005957.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTHFR | NM_005957.5 | c.1262G>T | p.Trp421Leu | missense_variant | 8/12 | ENST00000376590.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTHFR | ENST00000376590.9 | c.1262G>T | p.Trp421Leu | missense_variant | 8/12 | 1 | NM_005957.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152028Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461774Hom.: 0 Cov.: 38 AF XY: 0.0000138 AC XY: 10AN XY: 727186
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at