chr5-79030927-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013391.3(DMGDH):c.1589C>G(p.Ala530Gly) variant causes a missense change. The variant allele was found at a frequency of 0.288 in 1,613,572 control chromosomes in the GnomAD database, including 70,233 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9030 hom., cov: 32)

Exomes 𝑓: 0.28 ( 61203 hom. )

Consequence

DMGDH
NM_013391.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.09

Publications

37 publications found

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 Gene-Disease associations (from GenCC):

dimethylglycine dehydrogenase deficiency
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

DMGDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005518168).

BP6

Variant 5-79030927-G-C is Benign according to our data. Variant chr5-79030927-G-C is described in ClinVar as Benign. ClinVar VariationId is 380064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMGDH	NM_013391.3 link	c.1589C>G	p.Ala530Gly	missense_variant	Exon 10 of 16	ENST00000255189.8	NP_037523.2	Q9UI17-1B3KQ84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8 link	c.1589C>G	p.Ala530Gly	missense_variant	Exon 10 of 16	1	NM_013391.3	ENSP00000255189.3		Q9UI17-1

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50103

AN:

151884

Hom.:

9022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.311

GnomAD2 exomes

AF:

0.274

AC:

68891

AN:

251256

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.476

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.284

AC:

415222

AN:

1461570

Hom.:

61203

Cov.:

AF XY:

0.285

AC XY:

207060

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.477

AC:

15976

AN:

33470

American (AMR)

AF:

0.164

AC:

7331

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8398

AN:

26136

East Asian (EAS)

AF:

0.145

AC:

5750

AN:

39700

South Asian (SAS)

AF:

0.300

AC:

25842

AN:

86246

European-Finnish (FIN)

AF:

0.269

AC:

14392

AN:

53408

Middle Eastern (MID)

AF:

0.325

AC:

1877

AN:

5768

European-Non Finnish (NFE)

AF:

0.286

AC:

318507

AN:

1111744

Other (OTH)

AF:

0.284

AC:

17149

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

15206

30411

45617

60822

76028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10522

21044

31566

42088

52610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.330

AC:

50141

AN:

152002

Hom.:

9030

Cov.:

AF XY:

0.327

AC XY:

24307

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.477

AC:

19747

AN:

41430

American (AMR)

AF:

0.230

AC:

3510

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1051

AN:

3470

East Asian (EAS)

AF:

0.147

AC:

758

AN:

5166

South Asian (SAS)

AF:

0.290

AC:

1397

AN:

4812

European-Finnish (FIN)

AF:

0.279

AC:

2940

AN:

10554

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19828

AN:

67976

Other (OTH)

AF:

0.307

AC:

649

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1636

3272

4909

6545

8181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.277

Hom.:

4398

Bravo

AF:

0.329

TwinsUK

AF:

0.280

AC:

1040

ALSPAC

AF:

0.292

AC:

1125

ESP6500AA

AF:

0.465

AC:

2049

ESP6500EA

AF:

0.287

AC:

2467

ExAC

AF:

0.281

AC:

34078

Asia WGS

AF:

0.210

AC:

731

AN:

3478

EpiCase

AF:

0.301

EpiControl

AF:

0.304

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.080

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.2

N;.

PhyloP100

6.1

PrimateAI

Uncertain

0.63

PROVEAN

Benign

5.2

N;N

REVEL

Uncertain

0.31

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.086

MPC

0.14

ClinPred

0.0055

GERP RS

5.9

Varity_R

0.34

gMVP

0.84

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over