rs642013

Variant names:

• chr5-79011442-A-G
• rs642013
• NM_013391.3:c.2251-6035T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013391.3(DMGDH):​c.2251-6035T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,136 control chromosomes in the GnomAD database, including 37,110 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 0.70 (37110 hom., cov: 33)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.914
• Publications: 2 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMGDH	NM_013391.3	c.2251-6035T>C		intron_variant	Intron 14 of 15	ENST00000255189.8	NP_037523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8	c.2251-6035T>C		intron_variant	Intron 14 of 15	1	NM_013391.3	ENSP00000255189.3

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106069 AN: 152014 Hom.: 37068 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.698 AC: 106162 AN: 152136 Hom.: 37110 Cov.: 33 AF XY: 0.695 AC XY: 51703 AN XY: 74352

African (AFR) AF: 0.685 AC: 28419 AN: 41494

American (AMR) AF: 0.690 AC: 10540 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2329 AN: 3472

East Asian (EAS) AF: 0.732 AC: 3788 AN: 5176

South Asian (SAS) AF: 0.700 AC: 3373 AN: 4818

European-Finnish (FIN) AF: 0.691 AC: 7311 AN: 10586

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 48000 AN: 68000

Other (OTH) AF: 0.692 AC: 1461 AN: 2112

Alfa AF: 0.701 Hom.: 11660

Bravo AF: 0.697

Asia WGS AF: 0.747 AC: 2598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.68
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs642013; hg19: chr5-78307265;