rs2034899

chr5-79020365-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013391.3(DMGDH):c.2250+3906A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,106 control chromosomes in the GnomAD database, including 9,100 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 0.33 (9100 hom., cov: 32)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMGDH	NM_013391.3	c.2250+3906A>C		intron_variant		ENST00000255189.8
DMGDH	XM_011543355.3	c.*3566A>C		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000255189.8	c.2250+3906A>C		intron_variant		1	NM_013391.3	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50290 AN: 151986 Hom.: 9089 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50333 AN: 152106 Hom.: 9100 Cov.: 32 AF XY: 0.328 AC XY: 24373 AN XY: 74356

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.310

Alfa AF: 0.320 Hom.: 994

Bravo AF: 0.330

Asia WGS AF: 0.211 AC: 731 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.85

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

Other links and lift over

dbSNP: rs2034899; hg19: chr5-78316188;