ENST00000518707.1:n.129-14311T>G

Variant names:

• chr5-79135663-A-C
• rs955897
• ENST00000518707.1:n.129-14311T>G

Variant summary

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

The ENST00000518707.1(DMGDH):​n.129-14311T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,832 control chromosomes in the GnomAD database, including 13,890 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 0.42 (13890 hom., cov: 32)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518707.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	ENST00000518707.1	TSL:2	n.129-14311T>G		intron	N/A
	DMGDH	ENST00000520388.5	TSL:4	n.229-14311T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64434 AN: 151712 Hom.: 13879 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.425 AC: 64492 AN: 151832 Hom.: 13890 Cov.: 32 AF XY: 0.433 AC XY: 32123 AN XY: 74198

African (AFR) AF: 0.443 AC: 18326 AN: 41382

American (AMR) AF: 0.456 AC: 6943 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3466

East Asian (EAS) AF: 0.581 AC: 3002 AN: 5168

South Asian (SAS) AF: 0.567 AC: 2724 AN: 4804

European-Finnish (FIN) AF: 0.460 AC: 4844 AN: 10522

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25751 AN: 67938

Other (OTH) AF: 0.439 AC: 925 AN: 2108

Alfa AF: 0.179 Hom.: 313

Bravo AF: 0.424

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.9
DANN	Benign	0.72
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs955897; hg19: chr5-78431486;