5-79152282-C-G

Variant names:

• chr5-79152282-C-G
• rs1275103
• ENST00000518707.1:n.129-30930G>C

Variant summary

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

The ENST00000518707.1(DMGDH):​n.129-30930G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,008 control chromosomes in the GnomAD database, including 18,604 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 0.48 (18604 hom., cov: 32)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.129-30930G>C		intron	N/A
	DMGDH	ENST00000520388.5	TSL:4	n.229-30930G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73541 AN: 151890 Hom.: 18570 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.484 AC: 73639 AN: 152008 Hom.: 18604 Cov.: 32 AF XY: 0.489 AC XY: 36344 AN XY: 74290

African (AFR) AF: 0.627 AC: 26001 AN: 41438

American (AMR) AF: 0.482 AC: 7366 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1528 AN: 3472

East Asian (EAS) AF: 0.580 AC: 3003 AN: 5176

South Asian (SAS) AF: 0.571 AC: 2754 AN: 4826

European-Finnish (FIN) AF: 0.470 AC: 4954 AN: 10550

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26428 AN: 67966

Other (OTH) AF: 0.477 AC: 1005 AN: 2106

Alfa AF: 0.291 Hom.: 657

Bravo AF: 0.491

Asia WGS AF: 0.619 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		0.011

Splicing

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

Other links and lift over

dbSNP: rs1275103; hg19: chr5-78448105;