rs16876512

Variant names:

• chr5-79111438-C-T
• rs16876512
• ENST00000520388.5:n.492-7160G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520388.5(DMGDH):​n.492-7160G>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 11 publications found

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]

DMGDH Gene-Disease associations (from GenCC):

• dimethylglycine dehydrogenase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000520388.5	n.492-7160G>A		intron_variant	Intron 3 of 4	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

African (AFR) AF: 0.100 AC: 4159 AN: 41566

American (AMR) AF: 0.0672 AC: 1028 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4820

European-Finnish (FIN) AF: 0.0948 AC: 1005 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7339 AN: 68018

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.101 Hom.: 1280

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
PhyloP100		-0.012
PromoterAI		0.040	Neutral

Splicing

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

Other links and lift over

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