NM_013391.3:c.1194-2592A>G

Variant names:

• chr5-79036000-T-C
• rs185077
• NM_013391.3:c.1194-2592A>G

Variant summary

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

The NM_013391.3(DMGDH):​c.1194-2592A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,088 control chromosomes in the GnomAD database, including 17,955 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 0.48 (17955 hom., cov: 32)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 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.1194-2592A>G		intron	N/A	NP_037523.2	Q9UI17-1
	DMGDH	NR_104002.3		n.779-2592A>G		intron	N/A
	DMGDH	NR_104003.3		n.331-2592A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	ENST00000255189.8	TSL:1 MANE Select	c.1194-2592A>G		intron	N/A	ENSP00000255189.3	Q9UI17-1
	DMGDH	ENST00000523732.1	TSL:1	c.711-2592A>G		intron	N/A	ENSP00000430972.1	Q8TCC6
	DMGDH	ENST00000895914.1		c.1221-2592A>G		intron	N/A	ENSP00000565973.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73027 AN: 151970 Hom.: 17929 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.481 AC: 73095 AN: 152088 Hom.: 17955 Cov.: 32 AF XY: 0.481 AC XY: 35786 AN XY: 74346

African (AFR) AF: 0.387 AC: 16043 AN: 41484

American (AMR) AF: 0.542 AC: 8276 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1502 AN: 3472

East Asian (EAS) AF: 0.636 AC: 3293 AN: 5176

South Asian (SAS) AF: 0.468 AC: 2259 AN: 4824

European-Finnish (FIN) AF: 0.529 AC: 5585 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34337 AN: 67972

Other (OTH) AF: 0.482 AC: 1020 AN: 2114

Alfa AF: 0.494 Hom.: 11621

Bravo AF: 0.480

Asia WGS AF: 0.544 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.82
PhyloP100		0.13
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: rs185077; hg19: chr5-78331823;