rs5868949

Variant names:

• chr5-79069165-TGC-T
• rs5868949
• NM_013391.3:c.101+353_101+354delGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013391.3(DMGDH):​c.101+353_101+354delGC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14955 hom., cov: 0)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 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+353_101+354delGC		intron	N/A	NP_037523.2	Q9UI17-1
	DMGDH	NR_104002.3		n.155+353_155+354delGC		intron	N/A
	DMGDH	NR_104003.3		n.155+353_155+354delGC		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+353_101+354delGC		intron	N/A	ENSP00000255189.3	Q9UI17-1
	DMGDH	ENST00000895914.1		c.128+81_128+82delGC		intron	N/A	ENSP00000565973.1
	DMGDH	ENST00000895909.1		c.101+353_101+354delGC		intron	N/A	ENSP00000565968.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61466 AN: 151568 Hom.: 14948 Cov.: 0

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.405 AC: 61472 AN: 151686 Hom.: 14955 Cov.: 0 AF XY: 0.410 AC XY: 30379 AN XY: 74110

African (AFR) AF: 0.117 AC: 4847 AN: 41514

American (AMR) AF: 0.519 AC: 7911 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3464

East Asian (EAS) AF: 0.641 AC: 3285 AN: 5124

South Asian (SAS) AF: 0.462 AC: 2223 AN: 4810

European-Finnish (FIN) AF: 0.572 AC: 6000 AN: 10482

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34224 AN: 67756

Other (OTH) AF: 0.432 AC: 908 AN: 2104

Alfa AF: 0.433 Hom.: 1832

Bravo AF: 0.391

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56
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: rs5868949; hg19: chr5-78364988;