rs402701

Variant names:

• chr5-79034699-A-G
• rs402701
• NM_013391.3:c.1194-1291T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-79034699-A-G
• chr5-79034699-A-T

Variant summary

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

The NM_013391.3(DMGDH):​c.1194-1291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,006 control chromosomes in the GnomAD database, including 18,737 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 0.49 (18737 hom., cov: 32)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMGDH	NM_013391.3	c.1194-1291T>C		intron_variant	Intron 7 of 15	ENST00000255189.8	NP_037523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8	c.1194-1291T>C		intron_variant	Intron 7 of 15	1	NM_013391.3	ENSP00000255189.3
DMGDH	ENST00000523732.1	c.711-1291T>C		intron_variant	Intron 4 of 11	1		ENSP00000430972.1
DMGDH	ENST00000517853.5	n.277-1291T>C		intron_variant	Intron 2 of 9	2		ENSP00000428995.1
DMGDH	ENST00000518477.5	n.*428-1291T>C		intron_variant	Intron 4 of 11	2		ENSP00000427834.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74298 AN: 151888 Hom.: 18717 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.489 AC: 74354 AN: 152006 Hom.: 18737 Cov.: 32 AF XY: 0.489 AC XY: 36320 AN XY: 74294

African (AFR) AF: 0.610 AC: 25274 AN: 41452

American (AMR) AF: 0.407 AC: 6220 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1881 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1887 AN: 5162

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4820

European-Finnish (FIN) AF: 0.448 AC: 4720 AN: 10538

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30622 AN: 67968

Other (OTH) AF: 0.486 AC: 1026 AN: 2110

Alfa AF: 0.481 Hom.: 2197

Bravo AF: 0.487

Asia WGS AF: 0.436 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.6
DANN	Benign	0.82
PhyloP100		1.3
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: rs402701; hg19: chr5-78330522;