rs2236225
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005956.4(MTHFD1):c.1958G>A(p.Arg653Gln) variant causes a missense change. The variant allele was found at a frequency of 0.443 in 1,613,486 control chromosomes in the GnomAD database, including 162,717 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R653W) has been classified as Uncertain significance.
Frequency
Consequence
NM_005956.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTHFD1 | NM_005956.4 | c.1958G>A | p.Arg653Gln | missense_variant | 20/28 | ENST00000652337.1 | |
MTHFD1 | NM_001364837.1 | c.1958G>A | p.Arg653Gln | missense_variant | 20/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTHFD1 | ENST00000652337.1 | c.1958G>A | p.Arg653Gln | missense_variant | 20/28 | NM_005956.4 | P1 | ||
ENST00000609125.1 | n.112C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
ENST00000556640.1 | n.505+5926C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.387 AC: 58706AN: 151876Hom.: 12553 Cov.: 32
GnomAD3 exomes AF: 0.444 AC: 111611AN: 251462Hom.: 26100 AF XY: 0.448 AC XY: 60904AN XY: 135900
GnomAD4 exome AF: 0.449 AC: 656233AN: 1461492Hom.: 150163 Cov.: 47 AF XY: 0.451 AC XY: 328125AN XY: 727076
GnomAD4 genome AF: 0.386 AC: 58737AN: 151994Hom.: 12554 Cov.: 32 AF XY: 0.389 AC XY: 28908AN XY: 74282
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency, variant associated with elevated BMI, temporomandibular disorder, neural tube defects, and decreased risk for congenital heart defects. Overall, not convincing. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | This variant is associated with the following publications: (PMID: 24977710, 23685927, 12384833, 25525159, 16123074, 24368157, 18767138, 16552426, 21615938) - |
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Neural tube defects, folate-sensitive, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Mar 01, 2008 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at