Variant 5-79120593-C-T 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.477+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,506,308 control chromosomes in the GnomAD database, including 90,396 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 0.28 ( 7407 hom., cov: 33)

Exomes 𝑓: 0.34 ( 82989 hom. )

Consequence

BHMT
NM_001713.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.403

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 (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 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.477+52C>T		intron_variant		ENST00000274353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHMT	ENST00000274353.10 linkuse as main transcript	c.477+52C>T		intron_variant		1	NM_001713.3	P1

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42924

AN:

152044

Hom.:

7401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.349

AC:

62467

AN:

178910

Hom.:

11638

AF XY:

0.357

AC XY:

34179

AN XY:

95626

show subpopulations

Gnomad AFR exome

AF:

0.0633

Gnomad AMR exome

AF:

0.413

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.345

AC:

466746

AN:

1354146

Hom.:

82989

Cov.:

AF XY:

0.348

AC XY:

231904

AN XY:

667294

show subpopulations

Gnomad4 AFR exome

AF:

0.0556

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.423

Gnomad4 SAS exome

AF:

0.430

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.282

AC:

42937

AN:

152162

Hom.:

7407

Cov.:

AF XY:

0.292

AC XY:

21753

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0734

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.423

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.434

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.325

Hom.:

4609

Bravo

AF:

0.269

Asia WGS

AF:

0.413

AC:

1436

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.76

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