rs476620

Positions:

• chr5-79058623-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.277-2715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,002 control chromosomes in the GnomAD database, including 22,796 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 0.52 (22796 hom., cov: 32)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMGDH	NM_013391.3	c.277-2715C>T		intron_variant		ENST00000255189.8	NP_037523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8	c.277-2715C>T		intron_variant		1	NM_013391.3	ENSP00000255189	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79688 AN: 151884 Hom.: 22781 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.525 AC: 79728 AN: 152002 Hom.: 22796 Cov.: 32 AF XY: 0.527 AC XY: 39186 AN XY: 74294

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.675

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.535

Alfa AF: 0.594 Hom.: 26395

Bravo AF: 0.509

Asia WGS AF: 0.565 AC: 1961 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.59

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: rs476620; hg19: chr5-78354446;