Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005957(MTHFR):c.1959G>A(p.Thr653=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 152162 control chromosomes in the gnomAD Genomes database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Verdict is Benign. Variant got -21 ACMG points.
GnomAD3 genomes AF: 0.00183AC: 278AN: 152162Hom.: 4Cov.: 33 GnomAD3 exomes AF: 0.000474AC: 119AN: 251294Hom.: 1 AF XY: 0.000361AC XY: 49AN XY: 135832 GnomAD4 exome AF: 0.000244AC: 356AN: 1461858Hom.: 0 AF XY: 0.000223AC XY: 162AN XY: 727220
Submissions by phenotype
Schizophrenia;C1856058:Homocystinuria due to methylene tetrahydrofolate reductase deficiency;C1866558:Neural tube defects, folate-sensitive;C3160733:Thrombophilia due to thrombin defect
|Likely benign, criteria provided, single submitter||clinical testing||Fulgent Genetics, Fulgent Genetics||Nov 05, 2021||- -|
|Benign, criteria provided, single submitter||clinical testing||Eurofins Ntd Llc (ga)||Dec 27, 2016||- -|
Inborn genetic diseases
|Likely benign, criteria provided, single submitter||clinical testing||Ambry Genetics||Oct 21, 2022||This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -|
|Likely benign, criteria provided, single submitter||clinical testing||GeneDx||May 03, 2018||This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -|
Homocystinuria due to methylene tetrahydrofolate reductase deficiency
|Benign, criteria provided, single submitter||clinical testing||Invitae||Oct 31, 2022||- -|
Find out detailed SpliceAI scores and Pangolin per-transcript scores at