rs16876512

chr5-79111438-C-T

Variant summary

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

The ENST00000520388.5(DMGDH):n.492-7160G>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 0.0942 in 152,272 control chromosomes in the GnomAD database, including 724 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 0.094 (724 hom., cov: 33)
• Consequence: DMGDH ENST00000520388.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000520388.5	n.492-7160G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14326 AN: 152154 Hom.: 724 Cov.: 33

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0674

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0843

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

GnomAD4 genome AF: 0.0942 AC: 14347 AN: 152272 Hom.: 724 Cov.: 33 AF XY: 0.0920 AC XY: 6853 AN XY: 74456

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0672

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.0948

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0839

Alfa AF: 0.102 Hom.: 914

Bravo AF: 0.0912

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.1
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16876512; hg19: chr5-78407261; COSMIC: COSV57153885;