Variant rs3733890 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001713.3(BHMT):c.716G>A(p.Arg239Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,612,820 control chromosomes in the GnomAD database, including 69,618 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.28 ( 5975 hom., cov: 31)

Exomes 𝑓: 0.29 ( 63643 hom. )

Consequence

BHMT
NM_001713.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.86

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020504296).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHMT	NM_001713.3 linkuse as main transcript	c.716G>A	p.Arg239Gln	missense_variant	6/8	ENST00000274353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHMT	ENST00000274353.10 linkuse as main transcript	c.716G>A	p.Arg239Gln	missense_variant	6/8	1	NM_001713.3	P1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42017

AN:

151846

Hom.:

5975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.302

AC:

75970

AN:

251278

Hom.:

11846

AF XY:

0.302

AC XY:

41045

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.324

Gnomad SAS exome

AF:

0.289

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.298

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.293

AC:

427841

AN:

1460856

Hom.:

63643

Cov.:

AF XY:

0.293

AC XY:

212945

AN XY:

726532

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.271

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.277

AC:

42027

AN:

151964

Hom.:

5975

Cov.:

AF XY:

0.276

AC XY:

20510

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.341

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.240

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.302

Hom.:

14962

Bravo

AF:

0.285

TwinsUK

AF:

0.309

AC:

1144

ALSPAC

AF:

0.300

AC:

1155

ESP6500AA

AF:

0.222

AC:

980

ESP6500EA

AF:

0.300

AC:

2584

ExAC

AF:

0.295

AC:

35825

Asia WGS

AF:

0.273

AC:

947

AN:

3478

EpiCase

AF:

0.312

EpiControl

AF:

0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.16

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.058

Sift

Benign

0.051

T;T

Sift4G

Uncertain

0.022

D;D

Polyphen

0.0

B;P

Vest4

0.084

MPC

0.11

ClinPred

0.011

GERP RS

3.5

Varity_R

0.058

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over