rs2253262

chr5-79055813-A-Cchr5-79055813-A-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_013391.3(DMGDH):c.372T>G(p.Gly124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,579,890 control chromosomes in the GnomAD database, including 325,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31077 hom., cov: 32)
  • Exomes 𝑓: 0.64 (294171 hom.)
• Consequence: DMGDH NM_013391.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.573

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-79055813-A-C is Benign according to our data. Variant chr5-79055813-A-C is described in ClinVar as [Benign]. Clinvar id is 380019.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-79055813-A-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.573 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMGDH	NM_013391.3	c.372T>G	p.Gly124=	synonymous_variant	3/16	ENST00000255189.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000255189.8	c.372T>G	p.Gly124=	synonymous_variant	3/16	1	NM_013391.3	P1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96855 AN: 151910 Hom.: 31038 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.635

GnomAD3 exomes AF: 0.643 AC: 160556 AN: 249518 Hom.: 52115 AF XY: 0.644 AC XY: 86786 AN XY: 134814

Gnomad AFR exome AF: 0.604

Gnomad AMR exome AF: 0.633

Gnomad ASJ exome AF: 0.538

Gnomad EAS exome AF: 0.780

Gnomad SAS exome AF: 0.619

Gnomad FIN exome AF: 0.668

Gnomad NFE exome AF: 0.643

Gnomad OTH exome AF: 0.624

GnomAD4 exome AF: 0.640 AC: 913788 AN: 1427862 Hom.: 294171 Cov.: 27 AF XY: 0.640 AC XY: 455574 AN XY: 712294

Gnomad4 AFR exome AF: 0.596

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.540

Gnomad4 EAS exome AF: 0.764

Gnomad4 SAS exome AF: 0.623

Gnomad4 FIN exome AF: 0.664

Gnomad4 NFE exome AF: 0.640

Gnomad4 OTH exome AF: 0.641

GnomAD4 genome AF: 0.638 AC: 96943 AN: 152028 Hom.: 31077 Cov.: 32 AF XY: 0.639 AC XY: 47505 AN XY: 74324

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.639

Alfa AF: 0.631 Hom.: 37568

Bravo AF: 0.635

Asia WGS AF: 0.725 AC: 2524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	6.0
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2253262; hg19: chr5-78351636;