rs372541519

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001713.3(BHMT):c.47G>A(p.Arg16His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,611,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

BHMT
NM_001713.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

DMGDH links:

LOC124901012 (HGNC:):

LOC124901012 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.799

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.47G>A	p.Arg16His	missense	Exon 2 of 8	NP_001704.2	Q93088

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BHMT	ENST00000274353.10	TSL:1 MANE Select	c.47G>A	p.Arg16His	missense	Exon 2 of 8	ENSP00000274353.5	Q93088
BHMT	ENST00000910530.1		c.47G>A	p.Arg16His	missense	Exon 2 of 8	ENSP00000580589.1
BHMT	ENST00000910525.1		c.47G>A	p.Arg16His	missense	Exon 2 of 8	ENSP00000580584.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250198

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1459452

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

726072

show subpopulations

African (AFR)

AF:

0.0000599

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.0000699

AC:

AN:

85836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000342

AC:

AN:

1110662

Other (OTH)

AF:

0.0000332

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000550

EpiControl

AF:

0.0000596

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.76

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.3

PhyloP100

9.6

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.45

Sift

Uncertain

0.015

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.85

MVP

0.55

MPC

0.47

ClinPred

0.87

GERP RS

5.4

Varity_R

0.75

gMVP

0.91

Mutation Taster

=16/84

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over