rs617219

Positions:

• chr5-79133771-A-C

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, non coding transcript 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, non_coding_transcript
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000518707.1	n.129-12419T>G		intron_variant, non_coding_transcript_variant		2
DMGDH	ENST00000520388.5	n.229-12419T>G		intron_variant, non_coding_transcript_variant		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;