dbSNP rs16876527: BHMT:c.34-164T>C (chr5-79115603-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001713.3(BHMT):c.34-164T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 152,258 control chromosomes in the GnomAD database, including 227 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 0.052 ( 227 hom., cov: 32)

Consequence

BHMT
NM_001713.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

2 publications found

Variant links:

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]

BHMT links:

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)

DMGDH links:

LOC124901012 (HGNC:):

LOC124901012 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BHMT	NM_001713.3 link	c.34-164T>C		intron_variant	Intron 1 of 7	ENST00000274353.10	NP_001704.2	Q93088V9HWA4
LOC124901012	XR_007058837.1 link	n.80-305A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BHMT	ENST00000274353.10 link	c.34-164T>C		intron_variant	Intron 1 of 7	1	NM_001713.3	ENSP00000274353.5		Q93088

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7900

AN:

152140

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0779

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0426

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0801

Gnomad SAS

AF:

0.0833

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0584

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

GnomAD4 genome

AF:

0.0519

AC:

7903

AN:

152258

Hom.:

227

Cov.:

AF XY:

0.0522

AC XY:

3889

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0780

AC:

3238

AN:

41534

American (AMR)

AF:

0.0425

AC:

650

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

357

AN:

3472

East Asian (EAS)

AF:

0.0803

AC:

416

AN:

5180

South Asian (SAS)

AF:

0.0821

AC:

396

AN:

4822

European-Finnish (FIN)

AF:

0.0188

AC:

199

AN:

10604

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0367

AC:

2498

AN:

68030

Other (OTH)

AF:

0.0582

AC:

123

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

372

743

1115

1486

1858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0480

Hom.:

Bravo

AF:

0.0540

Asia WGS

AF:

0.108

AC:

375

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.3

(source)

DANN

Benign

0.87

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over