NM_001713.3:c.808+519A>T

Variant names:

• chr5-79126747-A-T
• rs10037045
• NM_001713.3:c.808+519A>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.808+519A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,806 control chromosomes in the GnomAD database, including 7,715 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 0.32 (7715 hom., cov: 31)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT	NM_001713.3	MANE Select	c.808+519A>T		intron	N/A	NP_001704.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT	ENST00000274353.10	TSL:1 MANE Select	c.808+519A>T		intron	N/A	ENSP00000274353.5
	BHMT	ENST00000524080.1	TSL:2	c.349+519A>T		intron	N/A	ENSP00000428240.1
	DMGDH	ENST00000518707.1	TSL:2	n.129-5395T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47954 AN: 151688 Hom.: 7705 Cov.: 31

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.316 AC: 47995 AN: 151806 Hom.: 7715 Cov.: 31 AF XY: 0.314 AC XY: 23288 AN XY: 74206

African (AFR) AF: 0.358 AC: 14786 AN: 41338

American (AMR) AF: 0.354 AC: 5401 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3466

East Asian (EAS) AF: 0.319 AC: 1645 AN: 5162

South Asian (SAS) AF: 0.281 AC: 1350 AN: 4802

European-Finnish (FIN) AF: 0.239 AC: 2520 AN: 10548

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20135 AN: 67924

Other (OTH) AF: 0.325 AC: 685 AN: 2106

Alfa AF: 0.158 Hom.: 273

Bravo AF: 0.330

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.61
PhyloP100		0.094
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: rs10037045; hg19: chr5-78422570;