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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901011	XR_007058835.1	n.214-3783G>C		intron_variant	Intron 1 of 1
LOC124901011	XR_007058836.1	n.213+8102G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000518707.1	n.128+8102G>C		intron_variant	Intron 1 of 2	2
DMGDH	ENST00000520388.5	n.228+8102G>C		intron_variant	Intron 1 of 4	4
DMGDH	ENST00000520855.1	n.196-3783G>C		intron_variant	Intron 1 of 2	3

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 v4.3

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

Other links and lift over

dbSNP: rs3829809; hg19: chr5-78523532; COSMIC: COSV72897594;