5-79005225-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_013391.3(DMGDH):c.2385+47_2385+48insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,611,422 control chromosomes in the GnomAD database, including 4,786 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (382 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4404 hom.)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.643

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 -10 ACMG points.

• BP6: Variant 5-79005225-G-GT is Benign according to our data. Variant chr5-79005225-G-GT is described in ClinVar as [Benign]. Clinvar id is 1285801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMGDH	NM_013391.3	c.2385+47_2385+48insA		intron_variant		ENST00000255189.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000255189.8	c.2385+47_2385+48insA		intron_variant		1	NM_013391.3	P1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10274 AN: 152186 Hom.: 383 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.0579

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0679

GnomAD3 exomes AF: 0.0723 AC: 18015 AN: 249328 Hom.: 658 AF XY: 0.0724 AC XY: 9751 AN XY: 134736

Gnomad AFR exome AF: 0.0457

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.0582

Gnomad EAS exome AF: 0.0653

Gnomad SAS exome AF: 0.0724

Gnomad FIN exome AF: 0.0861

Gnomad NFE exome AF: 0.0780

Gnomad OTH exome AF: 0.0738

GnomAD4 exome AF: 0.0759 AC: 110684 AN: 1459118 Hom.: 4404 Cov.: 31 AF XY: 0.0757 AC XY: 54976 AN XY: 725838

Gnomad4 AFR exome AF: 0.0443

Gnomad4 AMR exome AF: 0.0650

Gnomad4 ASJ exome AF: 0.0589

Gnomad4 EAS exome AF: 0.0624

Gnomad4 SAS exome AF: 0.0730

Gnomad4 FIN exome AF: 0.0847

Gnomad4 NFE exome AF: 0.0785

Gnomad4 OTH exome AF: 0.0681

GnomAD4 genome AF: 0.0675 AC: 10274 AN: 152304 Hom.: 382 Cov.: 32 AF XY: 0.0683 AC XY: 5088 AN XY: 74476

Gnomad4 AFR AF: 0.0470

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.0579

Gnomad4 SAS AF: 0.0724

Gnomad4 FIN AF: 0.0921

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0693 Hom.: 93

Bravo AF: 0.0638

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 16, 2019

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Computational scores

Source: dbNSFP v4.3

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: rs58764758; hg19: chr5-78301048;