rs694290

Variant names:

• chr5-79125957-G-A
• rs694290
• NM_001713.3:c.626-89G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-79125957-G-A
• chr5-79125957-G-C
• chr5-79125957-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001713.3(BHMT):​c.626-89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,371,326 control chromosomes in the GnomAD database, including 328,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34364 hom., cov: 30)
  • Exomes 𝑓: 0.69 (294352 hom.)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 5 publications found

Genes affected

BHMT (HGNC:1047): (betaine--homocysteine S-methyltransferase) This gene encodes a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. Defects in this gene could lead to hyperhomocyst(e)inemia, but such a defect has not yet been observed. [provided by RefSeq, Jul 2008]

DMGDH (HGNC:24475): (dimethylglycine dehydrogenase) This gene encodes an enzyme involved in the catabolism of choline, catalyzing the oxidative demethylation of dimethylglycine to form sarcosine. The enzyme is found as a monomer in the mitochondrial matrix, and uses flavin adenine dinucleotide and folate as cofactors. Mutation in this gene causes dimethylglycine dehydrogenase deficiency, characterized by a fishlike body odor, chronic muscle fatigue, and elevated levels of the muscle form of creatine kinase in serum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

DMGDH Gene-Disease associations (from GenCC):

• dimethylglycine dehydrogenase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001713.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT	NM_001713.3	MANE Select	c.626-89G>A		intron	N/A	NP_001704.2	Q93088

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT	ENST00000274353.10	TSL:1 MANE Select	c.626-89G>A		intron	N/A	ENSP00000274353.5	Q93088
	BHMT	ENST00000910530.1		c.626-92G>A		intron	N/A	ENSP00000580589.1
	BHMT	ENST00000910525.1		c.626-89G>A		intron	N/A	ENSP00000580584.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101254 AN: 151746 Hom.: 34339 Cov.: 30

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.701

GnomAD4 exome AF: 0.693 AC: 844553 AN: 1219462 Hom.: 294352 AF XY: 0.696 AC XY: 419229 AN XY: 602098

African (AFR) AF: 0.548 AC: 14865 AN: 27148

American (AMR) AF: 0.816 AC: 23015 AN: 28196

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 14841 AN: 19290

East Asian (EAS) AF: 0.760 AC: 28662 AN: 37694

South Asian (SAS) AF: 0.818 AC: 52526 AN: 64202

European-Finnish (FIN) AF: 0.678 AC: 33643 AN: 49616

Middle Eastern (MID) AF: 0.777 AC: 3760 AN: 4838

European-Non Finnish (NFE) AF: 0.680 AC: 637068 AN: 937276

Other (OTH) AF: 0.706 AC: 36173 AN: 51202

GnomAD4 genome AF: 0.667 AC: 101330 AN: 151864 Hom.: 34364 Cov.: 30 AF XY: 0.674 AC XY: 50038 AN XY: 74214

African (AFR) AF: 0.558 AC: 23087 AN: 41352

American (AMR) AF: 0.776 AC: 11862 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2658 AN: 3472

East Asian (EAS) AF: 0.804 AC: 4150 AN: 5162

South Asian (SAS) AF: 0.815 AC: 3919 AN: 4806

European-Finnish (FIN) AF: 0.699 AC: 7356 AN: 10530

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45941 AN: 67944

Other (OTH) AF: 0.699 AC: 1476 AN: 2112

Alfa AF: 0.676 Hom.: 115437

Bravo AF: 0.671

Asia WGS AF: 0.816 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.83
DANN	Benign	0.42
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs694290; hg19: chr5-78421780;