rs558133

Variant names:

• chr5-79129365-C-A
• rs558133
• NM_001713.3:c.1037+1382C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-79129365-C-A
• chr5-79129365-C-G
• chr5-79129365-C-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.1037+1382C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,088 control chromosomes in the GnomAD database, including 34,377 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 (34377 hom., cov: 32)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 18 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=-0.95).
• 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.1037+1382C>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.1037+1382C>A		intron	N/A	ENSP00000274353.5	Q93088
	BHMT	ENST00000910530.1		c.1034+1382C>A		intron	N/A	ENSP00000580589.1
	BHMT	ENST00000910525.1		c.1037+1382C>A		intron	N/A	ENSP00000580584.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101351 AN: 151970 Hom.: 34352 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.700

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.667 AC: 101427 AN: 152088 Hom.: 34377 Cov.: 32 AF XY: 0.674 AC XY: 50087 AN XY: 74328

African (AFR) AF: 0.557 AC: 23103 AN: 41464

American (AMR) AF: 0.776 AC: 11873 AN: 15302

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

East Asian (EAS) AF: 0.804 AC: 4156 AN: 5170

South Asian (SAS) AF: 0.815 AC: 3935 AN: 4826

European-Finnish (FIN) AF: 0.700 AC: 7388 AN: 10558

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

European-Non Finnish (NFE) AF: 0.676 AC: 45962 AN: 67982

Other (OTH) AF: 0.698 AC: 1471 AN: 2108

Alfa AF: 0.679 Hom.: 61275

Bravo AF: 0.670

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	-0.95
CADD	Benign	2.2
DANN	Benign	0.28
PhyloP100		0.15
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: rs558133; hg19: chr5-78425188;