5-79069161-T-C

Variant names:

• chr5-79069161-T-C
• rs4998017
• NM_013391.3:c.101+359A>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.101+359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,684 control chromosomes in the GnomAD database, including 15,561 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 0.43 (15561 hom., cov: 33)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 1 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=-0.91).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	NM_013391.3	MANE Select	c.101+359A>G		intron	N/A	NP_037523.2
	DMGDH	NR_104002.3		n.155+359A>G		intron	N/A
	DMGDH	NR_104003.3		n.155+359A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	ENST00000255189.8	TSL:1 MANE Select	c.101+359A>G		intron	N/A	ENSP00000255189.3
	DMGDH	ENST00000517853.5	TSL:2	n.101+359A>G		intron	N/A	ENSP00000428995.1
	DMGDH	ENST00000518477.5	TSL:2	n.101+359A>G		intron	N/A	ENSP00000427834.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65087 AN: 151566 Hom.: 15552 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.429 AC: 65108 AN: 151684 Hom.: 15561 Cov.: 33 AF XY: 0.434 AC XY: 32127 AN XY: 74102

African (AFR) AF: 0.200 AC: 8304 AN: 41472

American (AMR) AF: 0.527 AC: 8027 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1316 AN: 3462

East Asian (EAS) AF: 0.641 AC: 3283 AN: 5120

South Asian (SAS) AF: 0.462 AC: 2222 AN: 4812

European-Finnish (FIN) AF: 0.573 AC: 6012 AN: 10492

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34241 AN: 67778

Other (OTH) AF: 0.448 AC: 944 AN: 2108

Alfa AF: 0.448 Hom.: 1886

Bravo AF: 0.419

Asia WGS AF: 0.528 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.49
PhyloP100		0.011
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: rs4998017; hg19: chr5-78364984;