rs250513

chr5-79006373-C-T

Variant summary

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

The NM_013391.3(DMGDH):c.2251-966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,002 control chromosomes in the GnomAD database, including 3,396 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 0.21 (3396 hom., cov: 31)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMGDH	NM_013391.3	c.2251-966G>A		intron_variant		ENST00000255189.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000255189.8	c.2251-966G>A		intron_variant		1	NM_013391.3	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31574 AN: 151884 Hom.: 3391 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.208 AC: 31585 AN: 152002 Hom.: 3396 Cov.: 31 AF XY: 0.208 AC XY: 15447 AN XY: 74302

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.210

Alfa AF: 0.225 Hom.: 5326

Bravo AF: 0.211

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.7
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs250513; hg19: chr5-78302196;