rs642934

Variant names:

• chr5-79069021-C-A
• rs642934
• NM_013391.3:c.101+499G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-79069021-C-A
• chr5-79069021-C-G
• chr5-79069021-C-T

Variant summary

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

The NM_013391.3(DMGDH):​c.101+499G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,154 control chromosomes in the GnomAD database, including 40,824 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 0.73 (40824 hom., cov: 33)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 9 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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	NM_013391.3	MANE Select	c.101+499G>T		intron	N/A	NP_037523.2	Q9UI17-1
	DMGDH	NR_104002.3		n.155+499G>T		intron	N/A
	DMGDH	NR_104003.3		n.155+499G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	ENST00000255189.8	TSL:1 MANE Select	c.101+499G>T		intron	N/A	ENSP00000255189.3	Q9UI17-1
	DMGDH	ENST00000895914.1		c.128+227G>T		intron	N/A	ENSP00000565973.1
	DMGDH	ENST00000895909.1		c.101+499G>T		intron	N/A	ENSP00000565968.1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110469 AN: 152036 Hom.: 40792 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.727 AC: 110542 AN: 152154 Hom.: 40824 Cov.: 33 AF XY: 0.728 AC XY: 54135 AN XY: 74392

African (AFR) AF: 0.580 AC: 24062 AN: 41464

American (AMR) AF: 0.756 AC: 11560 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2354 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4104 AN: 5182

South Asian (SAS) AF: 0.758 AC: 3653 AN: 4822

European-Finnish (FIN) AF: 0.810 AC: 8583 AN: 10596

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53626 AN: 68018

Other (OTH) AF: 0.730 AC: 1540 AN: 2110

Alfa AF: 0.760 Hom.: 103993

Bravo AF: 0.715

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		0.12
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: rs642934; hg19: chr5-78364844;