Variant chr5-79077608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_017614.5(BHMT2):c.162C>T(p.Asp54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,612,500 control chromosomes in the GnomAD database, including 284,133 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 0.52 ( 22139 hom., cov: 29)

Exomes 𝑓: 0.59 ( 261994 hom. )

Consequence

BHMT2
NM_017614.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

BHMT2 (HGNC:1048): (betaine--homocysteine S-methyltransferase 2) Homocysteine is a sulfur-containing amino acid that plays a crucial role in methylation reactions. Transfer of the methyl group from betaine to homocysteine creates methionine, which donates the methyl group to methylate DNA, proteins, lipids, and other intracellular metabolites. The protein encoded by this gene is one of two methyl transferases that can catalyze the transfer of the methyl group from betaine to homocysteine. Anomalies in homocysteine metabolism have been implicated in disorders ranging from vascular disease to neural tube birth defects such as spina bifida. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

BHMT2 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHMT2	NM_017614.5 linkuse as main transcript	c.162C>T	p.Asp54=	synonymous_variant	2/8	ENST00000255192.8
BHMT2	NM_001178005.2 linkuse as main transcript	c.162C>T	p.Asp54=	synonymous_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHMT2	ENST00000255192.8 linkuse as main transcript	c.162C>T	p.Asp54=	synonymous_variant	2/8	1	NM_017614.5	P1	Q9H2M3-1

Frequencies

GnomAD3 genomes

AF:

0.519

AC:

78748

AN:

151618

Hom.:

22127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.769

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.521

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.574

AC:

143761

AN:

250584

Hom.:

42613

AF XY:

0.577

AC XY:

78119

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.599

Gnomad ASJ exome

AF:

0.440

Gnomad EAS exome

AF:

0.628

Gnomad SAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.663

Gnomad NFE exome

AF:

0.613

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.595

AC:

868680

AN:

1460762

Hom.:

261994

Cov.:

AF XY:

0.593

AC XY:

430866

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.262

Gnomad4 AMR exome

AF:

0.591

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.567

Gnomad4 SAS exome

AF:

0.512

Gnomad4 FIN exome

AF:

0.660

Gnomad4 NFE exome

AF:

0.614

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.519

AC:

78794

AN:

151738

Hom.:

22139

Cov.:

AF XY:

0.522

AC XY:

38732

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.595

Gnomad4 ASJ

AF:

0.448

Gnomad4 EAS

AF:

0.612

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.611

Gnomad4 OTH

AF:

0.529

Alfa

AF:

0.577

Hom.:

42335

Bravo

AF:

0.504

Asia WGS

AF:

0.548

AC:

1906

AN:

3478

EpiCase

AF:

0.601

EpiControl

AF:

0.606

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.020

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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