5-79005503-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_013391.3(DMGDH):c.2251-96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,501,208 control chromosomes in the GnomAD database, including 4,564 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: 32)
  • Exomes 𝑓: 0.077 (4175 hom.)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.915

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=-0.44).
• BP6: Variant 5-79005503-A-G is Benign according to our data. Variant chr5-79005503-A-G is described in ClinVar as [Benign]. Clinvar id is 1252301.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.2251-96T>C		intron_variant		ENST00000255189.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMGDH	ENST00000255189.8	c.2251-96T>C		intron_variant		1	NM_013391.3	P1

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10543 AN: 152164 Hom.: 389 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0619

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.0730

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0694

GnomAD4 exome AF: 0.0773 AC: 104208 AN: 1348928 Hom.: 4175 AF XY: 0.0770 AC XY: 51786 AN XY: 672572

Gnomad4 AFR exome AF: 0.0520

Gnomad4 AMR exome AF: 0.0660

Gnomad4 ASJ exome AF: 0.0593

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.0741

Gnomad4 FIN exome AF: 0.0851

Gnomad4 NFE exome AF: 0.0799

Gnomad4 OTH exome AF: 0.0696

GnomAD4 genome AF: 0.0693 AC: 10548 AN: 152280 Hom.: 389 Cov.: 32 AF XY: 0.0703 AC XY: 5232 AN XY: 74466

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: 0.0919

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0706

Alfa AF: 0.0701 Hom.: 92

Bravo AF: 0.0659

Asia WGS AF: 0.0840 AC: 292 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	7.5
Dann	Benign	0.72

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: rs41272264; hg19: chr5-78301326;