rs642431

Variant names:

• chr5-79068864-C-A
• rs642431
• NM_013391.3:c.101+656G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-79068864-C-A
• chr5-79068864-C-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+656G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,094 control chromosomes in the GnomAD database, including 39,568 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 0.71 (39568 hom., cov: 33)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMGDH	NM_013391.3	c.101+656G>T		intron_variant	Intron 1 of 15	ENST00000255189.8	NP_037523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8	c.101+656G>T		intron_variant	Intron 1 of 15	1	NM_013391.3	ENSP00000255189.3

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108184 AN: 151976 Hom.: 39544 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.712 AC: 108243 AN: 152094 Hom.: 39568 Cov.: 33 AF XY: 0.713 AC XY: 53046 AN XY: 74378

African (AFR) AF: 0.528 AC: 21873 AN: 41448

American (AMR) AF: 0.751 AC: 11463 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2352 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4105 AN: 5184

South Asian (SAS) AF: 0.758 AC: 3652 AN: 4816

European-Finnish (FIN) AF: 0.811 AC: 8589 AN: 10592

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53632 AN: 68000

Other (OTH) AF: 0.719 AC: 1518 AN: 2112

Alfa AF: 0.766 Hom.: 69027

Bravo AF: 0.699

Asia WGS AF: 0.735 AC: 2556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.56
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: rs642431; hg19: chr5-78364687;