rs585800

Variant names:

• chr5-79131385-T-A
• rs585800
• NM_001713.3:c.*269T>A

Variant summary

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

The NM_001713.3(BHMT):​c.*269T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 319,430 control chromosomes in the GnomAD database, including 100,039 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 0.81 (50864 hom., cov: 32)
  • Exomes 𝑓: 0.76 (49175 hom.)
• Consequence: BHMT NM_001713.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 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.*269T>A		3_prime_UTR	Exon 8 of 8	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.*269T>A		3_prime_UTR	Exon 8 of 8	ENSP00000274353.5	Q93088
	BHMT	ENST00000910530.1		c.*269T>A		3_prime_UTR	Exon 8 of 8	ENSP00000580589.1
	BHMT	ENST00000910525.1		c.*269T>A		3_prime_UTR	Exon 8 of 8	ENSP00000580584.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123228 AN: 152056 Hom.: 50798 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.830

GnomAD4 exome AF: 0.763 AC: 127595 AN: 167254 Hom.: 49175 Cov.: 3 AF XY: 0.765 AC XY: 66530 AN XY: 86940

African (AFR) AF: 0.950 AC: 4655 AN: 4898

American (AMR) AF: 0.856 AC: 4910 AN: 5738

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 5055 AN: 5944

East Asian (EAS) AF: 0.882 AC: 10727 AN: 12158

South Asian (SAS) AF: 0.867 AC: 8993 AN: 10372

European-Finnish (FIN) AF: 0.689 AC: 7119 AN: 10332

Middle Eastern (MID) AF: 0.865 AC: 675 AN: 780

European-Non Finnish (NFE) AF: 0.725 AC: 77327 AN: 106636

Other (OTH) AF: 0.782 AC: 8134 AN: 10396

GnomAD4 genome AF: 0.811 AC: 123355 AN: 152176 Hom.: 50864 Cov.: 32 AF XY: 0.813 AC XY: 60510 AN XY: 74398

African (AFR) AF: 0.953 AC: 39600 AN: 41556

American (AMR) AF: 0.851 AC: 13024 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4713 AN: 5174

South Asian (SAS) AF: 0.858 AC: 4133 AN: 4816

European-Finnish (FIN) AF: 0.712 AC: 7528 AN: 10566

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48640 AN: 67982

Other (OTH) AF: 0.831 AC: 1753 AN: 2110

Alfa AF: 0.756 Hom.: 5494

Bravo AF: 0.830

Asia WGS AF: 0.903 AC: 3139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.65
PhyloP100		0.034
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: rs585800; hg19: chr5-78427208;