rs2461248

Positions:

• chr5-79104608-A-T

Variant summary

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

The ENST00000520388.5(DMGDH):​n.492-330T>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,986 control chromosomes in the GnomAD database, including 15,317 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 0.41 (15317 hom., cov: 31)
• Consequence: DMGDH ENST00000520388.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000520388.5	n.492-330T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62581 AN: 151868 Hom.: 15310 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.412 AC: 62591 AN: 151986 Hom.: 15317 Cov.: 31 AF XY: 0.417 AC XY: 30932 AN XY: 74242

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.435

Alfa AF: 0.440 Hom.: 1942

Bravo AF: 0.397

Asia WGS AF: 0.505 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2461248; hg19: chr5-78400431;