chr5-79020365-T-G

Variant names:

• chr5-79020365-T-G
• rs2034899
• NM_013391.3:c.2250+3906A>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.2250+3906A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,106 control chromosomes in the GnomAD database, including 9,100 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 0.33 (9100 hom., cov: 32)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 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.2250+3906A>C		intron	N/A	NP_037523.2	Q9UI17-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	ENST00000255189.8	TSL:1 MANE Select	c.2250+3906A>C		intron	N/A	ENSP00000255189.3	Q9UI17-1
	DMGDH	ENST00000895914.1		c.2277+3906A>C		intron	N/A	ENSP00000565973.1
	DMGDH	ENST00000895909.1		c.2157+3906A>C		intron	N/A	ENSP00000565968.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50290 AN: 151986 Hom.: 9089 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.331 AC: 50333 AN: 152106 Hom.: 9100 Cov.: 32 AF XY: 0.328 AC XY: 24373 AN XY: 74356

African (AFR) AF: 0.480 AC: 19914 AN: 41480

American (AMR) AF: 0.232 AC: 3539 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3468

East Asian (EAS) AF: 0.149 AC: 772 AN: 5174

South Asian (SAS) AF: 0.289 AC: 1393 AN: 4814

European-Finnish (FIN) AF: 0.278 AC: 2940 AN: 10582

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19808 AN: 67982

Other (OTH) AF: 0.310 AC: 655 AN: 2116

Alfa AF: 0.312 Hom.: 2259

Bravo AF: 0.330

Asia WGS AF: 0.211 AC: 731 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.032
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: rs2034899; hg19: chr5-78316188;