Variant chr5-79121335-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001713.3(BHMT):c.595G>A(p.Gly199Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00749 in 1,614,174 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0055 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0077 ( 63 hom. )

Consequence

BHMT
NM_001713.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01422286).

BP6

Variant 5-79121335-G-A is Benign according to our data. Variant chr5-79121335-G-A is described in ClinVar as [Benign]. Clinvar id is 774306.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHMT	NM_001713.3 linkuse as main transcript	c.595G>A	p.Gly199Ser	missense_variant	5/8	ENST00000274353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHMT	ENST00000274353.10 linkuse as main transcript	c.595G>A	p.Gly199Ser	missense_variant	5/8	1	NM_001713.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

838

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00575

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00879

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00476

AC:

1196

AN:

251424

Hom.:

AF XY:

0.00460

AC XY:

625

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.00531

Gnomad NFE exome

AF:

0.00788

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00770

AC:

11258

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

5497

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00217

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.00580

Gnomad4 NFE exome

AF:

0.00923

Gnomad4 OTH exome

AF:

0.00575

GnomAD4 genome

AF:

0.00551

AC:

839

AN:

152332

Hom.:

Cov.:

AF XY:

0.00530

AC XY:

395

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00627

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00575

Gnomad4 NFE

AF:

0.00881

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00709

Hom.:

Bravo

AF:

0.00503

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00440

AC:

534

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00796

EpiControl

AF:

0.00812

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.021

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.29

Sift

Benign

0.050

Sift4G

Uncertain

0.058

Polyphen

0.98

Vest4

0.81

MVP

0.48

MPC

0.16

ClinPred

0.064

GERP RS

5.3

Varity_R

0.71

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over