rs6877474

Positions:

• chr5-79068984-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000255189.8(DMGDH):​c.101+536A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 152,358 control chromosomes in the GnomAD database, including 10 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 0.0076 (10 hom., cov: 33)
• Consequence: DMGDH ENST00000255189.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00759 (1157/152358) while in subpopulation AFR AF= 0.0261 (1085/41574). AF 95% confidence interval is 0.0248. There are 10 homozygotes in gnomad4. There are 548 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMGDH	NM_013391.3	c.101+536A>C		intron_variant		ENST00000255189.8	NP_037523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8	c.101+536A>C		intron_variant		1	NM_013391.3	ENSP00000255189	P1

Frequencies

GnomAD3 genomes AF: 0.00756 AC: 1151 AN: 152240 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00621

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

GnomAD4 genome AF: 0.00759 AC: 1157 AN: 152358 Hom.: 10 Cov.: 33 AF XY: 0.00736 AC XY: 548 AN XY: 74506

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00385 Hom.: 4

Bravo AF: 0.00848

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.74
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6877474; hg19: chr5-78364807;