rs617219

Variant names:

• chr5-79133771-A-C
• rs617219
• ENST00000518707.1:n.129-12419T>G

Variant summary

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

The ENST00000518707.1(DMGDH):​n.129-12419T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,048 control chromosomes in the GnomAD database, including 10,178 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 0.36 (10178 hom., cov: 32)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 8 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

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 (SAS) allele frequency at 95% confidence interval = 0.433 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.129-12419T>G		intron	N/A
	DMGDH	ENST00000520388.5	TSL:4	n.229-12419T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55173 AN: 151928 Hom.: 10172 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.363 AC: 55214 AN: 152048 Hom.: 10178 Cov.: 32 AF XY: 0.369 AC XY: 27428 AN XY: 74304

African (AFR) AF: 0.301 AC: 12466 AN: 41468

American (AMR) AF: 0.429 AC: 6551 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1259 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2158 AN: 5168

South Asian (SAS) AF: 0.449 AC: 2165 AN: 4820

European-Finnish (FIN) AF: 0.443 AC: 4671 AN: 10554

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24638 AN: 67968

Other (OTH) AF: 0.363 AC: 768 AN: 2114

Alfa AF: 0.357 Hom.: 3196

Bravo AF: 0.359

Asia WGS AF: 0.430 AC: 1495 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	0.19
DANN	Benign	0.40
PhyloP100		-1.7

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: rs617219;

hg19: chr5-78429594;