rs617219

Variant names:

• chr5-79133771-A-C
• rs617219
• ENST00000518707.1:n.129-12419T>G

Variant summary

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

The ENST00000518707.1(DMGDH):​n.129-12419T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,048 control chromosomes in the GnomAD database, including 10,178 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 0.36 (10178 hom., cov: 32)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000518707.1	n.129-12419T>G		intron_variant	Intron 1 of 2	2
DMGDH	ENST00000520388.5	n.229-12419T>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55173 AN: 151928 Hom.: 10172 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.363 AC: 55214 AN: 152048 Hom.: 10178 Cov.: 32 AF XY: 0.369 AC XY: 27428 AN XY: 74304

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.363

Alfa AF: 0.358 Hom.: 1642

Bravo AF: 0.359

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.19
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs617219; hg19: chr5-78429594;