rs3829809

Variant names:

• chr5-79227709-C-G
• rs3829809
• ENST00000518707.1:n.128+8102G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-79227709-C-G
• chr5-79227709-C-T

Variant summary

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

The ENST00000518707.1(DMGDH):​n.128+8102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,180 control chromosomes in the GnomAD database, including 8,032 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 0.30 (8032 hom., cov: 32)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 6 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

LOC124901011 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.432 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMGDH	ENST00000518707.1	TSL:2	n.128+8102G>C		intron	N/A
	DMGDH	ENST00000520388.5	TSL:4	n.228+8102G>C		intron	N/A
	DMGDH	ENST00000520855.1	TSL:3	n.196-3783G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45044 AN: 152062 Hom.: 8028 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.296 AC: 45053 AN: 152180 Hom.: 8032 Cov.: 32 AF XY: 0.305 AC XY: 22687 AN XY: 74366

African (AFR) AF: 0.0855 AC: 3554 AN: 41578

American (AMR) AF: 0.402 AC: 6146 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3468

East Asian (EAS) AF: 0.431 AC: 2227 AN: 5170

South Asian (SAS) AF: 0.448 AC: 2158 AN: 4822

European-Finnish (FIN) AF: 0.436 AC: 4595 AN: 10550

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23932 AN: 67984

Other (OTH) AF: 0.318 AC: 672 AN: 2112

Alfa AF: 0.314 Hom.: 1011

Bravo AF: 0.284

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.68
PhyloP100		-0.46

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3829809;

hg19: chr5-78523532;

COSMIC: COSV72897594;