5-79028332-TCA-T

Position:

• chr5-79028332-TCA-T

Variant summary

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

The NM_013391.3(DMGDH):​c.2032+99_2032+100del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,049,922 control chromosomes in the GnomAD database, including 310 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (31 hom., cov: 32)
  • Exomes 𝑓: 0.018 (279 hom.)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.399

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 5-79028332-TCA-T is Benign according to our data. Variant chr5-79028332-TCA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMGDH	NM_013391.3	c.2032+99_2032+100del		intron_variant		ENST00000255189.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000255189.8	c.2032+99_2032+100del		intron_variant		1	NM_013391.3	P1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2863 AN: 152160 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00968

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0200

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.0176 AC: 15821 AN: 897644 Hom.: 279 AF XY: 0.0195 AC XY: 9040 AN XY: 462816

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.00797

Gnomad4 ASJ exome AF: 0.0135

Gnomad4 EAS exome AF: 0.0140

Gnomad4 SAS exome AF: 0.0652

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.0134

Gnomad4 OTH exome AF: 0.0188

GnomAD4 genome AF: 0.0188 AC: 2869 AN: 152278 Hom.: 31 Cov.: 32 AF XY: 0.0198 AC XY: 1472 AN XY: 74464

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.00967

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.0200

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0139 Hom.: 1

Bravo AF: 0.0177

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 02, 2019

- -

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: rs201976488; hg19: chr5-78324155;