chr5-79140388-C-T

Variant names:

• chr5-79140388-C-T
• rs1915706
• ENST00000518707.1:n.129-19036G>A

Variant summary

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

The ENST00000518707.1(DMGDH):​n.129-19036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 151,936 control chromosomes in the GnomAD database, including 20,565 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 0.50 (20565 hom., cov: 32)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 14 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 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.129-19036G>A		intron	N/A
	DMGDH	ENST00000520388.5	TSL:4	n.229-19036G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76585 AN: 151818 Hom.: 20520 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.505 AC: 76691 AN: 151936 Hom.: 20565 Cov.: 32 AF XY: 0.511 AC XY: 37932 AN XY: 74272

African (AFR) AF: 0.670 AC: 27758 AN: 41414

American (AMR) AF: 0.502 AC: 7667 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3468

East Asian (EAS) AF: 0.772 AC: 3979 AN: 5154

South Asian (SAS) AF: 0.601 AC: 2884 AN: 4802

European-Finnish (FIN) AF: 0.459 AC: 4846 AN: 10550

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26256 AN: 67960

Other (OTH) AF: 0.500 AC: 1050 AN: 2100

Alfa AF: 0.450 Hom.: 27549

Bravo AF: 0.517

Asia WGS AF: 0.710 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.21
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs1915706; hg19: chr5-78436211;