Variant 5-79005431-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_013391.3(DMGDH):c.2251-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,613,844 control chromosomes in the GnomAD database, including 628 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 64 hom., cov: 32)

Exomes 𝑓: 0.025 ( 564 hom. )

Consequence

DMGDH
NM_013391.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.11

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-79005431-G-A is Benign according to our data. Variant chr5-79005431-G-A is described in ClinVar as [Benign]. Clinvar id is 1241076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0204 (3100/152330) while in subpopulation NFE AF= 0.0286 (1948/68030). AF 95% confidence interval is 0.0276. There are 64 homozygotes in gnomad4. There are 1593 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMGDH	NM_013391.3 linkuse as main transcript	c.2251-24C>T		intron_variant		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.2251-24C>T		intron_variant		1	NM_013391.3	ENSP00000255189.3		Q9UI17-1

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3101

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00502

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0668

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0286

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0199

AC:

4982

AN:

250894

Hom.:

AF XY:

0.0194

AC XY:

2625

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00357

Gnomad AMR exome

AF:

0.00580

Gnomad ASJ exome

AF:

0.0128

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000622

Gnomad FIN exome

AF:

0.0591

Gnomad NFE exome

AF:

0.0280

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0250

AC:

36511

AN:

1461514

Hom.:

564

Cov.:

AF XY:

0.0243

AC XY:

17677

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.00353

Gnomad4 AMR exome

AF:

0.00600

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000754

Gnomad4 FIN exome

AF:

0.0573

Gnomad4 NFE exome

AF:

0.0284

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0204

AC:

3100

AN:

152330

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1593

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00500

Gnomad4 AMR

AF:

0.0101

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0668

Gnomad4 NFE

AF:

0.0286

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0172

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 26, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.75

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over