Variant rs2253262 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013391.3(DMGDH):c.372T>G(p.Gly124Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,579,890 control chromosomes in the GnomAD database, including 325,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31077 hom., cov: 32)

Exomes 𝑓: 0.64 ( 294171 hom. )

Consequence

DMGDH
NM_013391.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.573

Variant links:

Genes affected

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:

DMGDH (HGNC:):

DMGDH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 5-79055813-A-C is Benign according to our data. Variant chr5-79055813-A-C is described in ClinVar as [Benign]. Clinvar id is 380019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-79055813-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.573 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMGDH	NM_013391.3 linkuse as main transcript	c.372T>G	p.Gly124Gly	synonymous_variant	3/16	ENST00000255189.8	NP_037523.2	Q9UI17-1B3KQ84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8 linkuse as main transcript	c.372T>G	p.Gly124Gly	synonymous_variant	3/16	1	NM_013391.3	ENSP00000255189.3		Q9UI17-1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96855

AN:

151910

Hom.:

31038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.635

GnomAD3 exomes

AF:

0.643

AC:

160556

AN:

249518

Hom.:

52115

AF XY:

0.644

AC XY:

86786

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.604

Gnomad AMR exome

AF:

0.633

Gnomad ASJ exome

AF:

0.538

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.619

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.624

GnomAD4 exome

AF:

0.640

AC:

913788

AN:

1427862

Hom.:

294171

Cov.:

AF XY:

0.640

AC XY:

455574

AN XY:

712294

show subpopulations

Gnomad4 AFR exome

AF:

0.596

Gnomad4 AMR exome

AF:

0.627

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.764

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.664

Gnomad4 NFE exome

AF:

0.640

Gnomad4 OTH exome

AF:

0.641

GnomAD4 genome

AF:

0.638

AC:

96943

AN:

152028

Hom.:

31077

Cov.:

AF XY:

0.639

AC XY:

47505

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.605

Gnomad4 AMR

AF:

0.652

Gnomad4 ASJ

AF:

0.549

Gnomad4 EAS

AF:

0.779

Gnomad4 SAS

AF:

0.629

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.640

Gnomad4 OTH

AF:

0.639

Alfa

AF:

0.631

Hom.:

37568

Bravo

AF:

0.635

Asia WGS

AF:

0.725

AC:

2524

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.0

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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