chr5-79005540-T-A

Position:

• chr5-79005540-T-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_013391.3(DMGDH):​c.2251-133A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,246,906 control chromosomes in the GnomAD database, including 3,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (389 hom., cov: 33)
  • Exomes 𝑓: 0.074 (3200 hom.)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.832

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 5-79005540-T-A is Benign according to our data. Variant chr5-79005540-T-A is described in ClinVar as [Benign]. Clinvar id is 1276841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
DMGDH	NM_013391.3	c.2251-133A>T		intron_variant		ENST00000255189.8	NP_037523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8	c.2251-133A>T		intron_variant		1	NM_013391.3	ENSP00000255189	P1

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10540 AN: 152200 Hom.: 389 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0680

GnomAD4 exome AF: 0.0736 AC: 80572 AN: 1094588 Hom.: 3200 AF XY: 0.0736 AC XY: 40705 AN XY: 552970

Gnomad4 AFR exome AF: 0.0517

Gnomad4 AMR exome AF: 0.0662

Gnomad4 ASJ exome AF: 0.0584

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.0735

Gnomad4 FIN exome AF: 0.0847

Gnomad4 NFE exome AF: 0.0757

Gnomad4 OTH exome AF: 0.0659

GnomAD4 genome AF: 0.0692 AC: 10545 AN: 152318 Hom.: 389 Cov.: 33 AF XY: 0.0702 AC XY: 5229 AN XY: 74488

Gnomad4 AFR AF: 0.0534

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.0727

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.0692

Alfa AF: 0.0338 Hom.: 26

Bravo AF: 0.0659

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.73

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: rs41272266; hg19: chr5-78301363;