rs644191

Positions:

• chr5-79069264-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013391.3(DMGDH):​c.101+256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,270 control chromosomes in the GnomAD database, including 52,888 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 0.83 (52888 hom., cov: 33)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMGDH	NM_013391.3	c.101+256C>T		intron_variant		ENST00000255189.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000255189.8	c.101+256C>T		intron_variant		1	NM_013391.3	P1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126656 AN: 152152 Hom.: 52830 Cov.: 33

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.833 AC: 126773 AN: 152270 Hom.: 52888 Cov.: 33 AF XY: 0.832 AC XY: 61955 AN XY: 74446

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.829

Alfa AF: 0.820 Hom.: 12750

Bravo AF: 0.833

Asia WGS AF: 0.903 AC: 3140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs644191; hg19: chr5-78365087;