5-79058124-C-T

Variant names:

• chr5-79058124-C-T
• rs7705204
• NM_013391.3:c.277-2216G>A

Variant summary

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

The NM_013391.3(DMGDH):​c.277-2216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 152,232 control chromosomes in the GnomAD database, including 867 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 0.071 (867 hom., cov: 32)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 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.277-2216G>A		intron	N/A	NP_037523.2
	DMGDH	NR_104002.3		n.330+5489G>A		intron	N/A
	DMGDH	NR_104003.3		n.330+5489G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	ENST00000255189.8	TSL:1 MANE Select	c.277-2216G>A		intron	N/A	ENSP00000255189.3
	DMGDH	ENST00000895914.1		c.304-2216G>A		intron	N/A	ENSP00000565973.1
	DMGDH	ENST00000895909.1		c.184-2216G>A		intron	N/A	ENSP00000565968.1

Frequencies

GnomAD3 genomes AF: 0.0713 AC: 10844 AN: 152114 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0713 AC: 10858 AN: 152232 Hom.: 867 Cov.: 32 AF XY: 0.0708 AC XY: 5269 AN XY: 74418

African (AFR) AF: 0.181 AC: 7522 AN: 41526

American (AMR) AF: 0.0382 AC: 584 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0815 AC: 283 AN: 3472

East Asian (EAS) AF: 0.139 AC: 723 AN: 5184

South Asian (SAS) AF: 0.104 AC: 501 AN: 4814

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0150 AC: 1021 AN: 68018

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0318 Hom.: 377

Bravo AF: 0.0780

Asia WGS AF: 0.145 AC: 506 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	1.8
DANN	Benign	0.58
PhyloP100		-0.55
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: rs7705204; hg19: chr5-78353947;