5-79113237-C-T

Variant names:

• chr5-79113237-C-T
• rs651852
• NM_001713.3:c.33+1319C>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.33+1319C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,976 control chromosomes in the GnomAD database, including 14,765 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 0.42 (14765 hom., cov: 32)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 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.33+1319C>T		intron	N/A	NP_001704.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT	ENST00000274353.10	TSL:1 MANE Select	c.33+1319C>T		intron	N/A	ENSP00000274353.5
	BHMT	ENST00000910530.1		c.33+1319C>T		intron	N/A	ENSP00000580589.1
	BHMT	ENST00000910525.1		c.33+1319C>T		intron	N/A	ENSP00000580584.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63403 AN: 151858 Hom.: 14757 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.417 AC: 63428 AN: 151976 Hom.: 14765 Cov.: 32 AF XY: 0.422 AC XY: 31373 AN XY: 74274

African (AFR) AF: 0.197 AC: 8153 AN: 41442

American (AMR) AF: 0.508 AC: 7764 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1291 AN: 3464

East Asian (EAS) AF: 0.607 AC: 3129 AN: 5156

South Asian (SAS) AF: 0.443 AC: 2134 AN: 4816

European-Finnish (FIN) AF: 0.571 AC: 6028 AN: 10562

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.490 AC: 33283 AN: 67950

Other (OTH) AF: 0.430 AC: 908 AN: 2114

Alfa AF: 0.448 Hom.: 3154

Bravo AF: 0.404

Asia WGS AF: 0.499 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs651852; hg19: chr5-78409060;