rs248386

Variant names:

• chr5-79034404-C-A
• rs248386
• NM_013391.3:c.1194-996G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-79034404-C-A
• chr5-79034404-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013391.3(DMGDH):​c.1194-996G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 151,958 control chromosomes in the GnomAD database, including 1,836 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1836 hom., cov: 32)
• Consequence: DMGDH NM_013391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 15 publications found

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]

DMGDH Gene-Disease associations (from GenCC):

• dimethylglycine dehydrogenase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMGDH	NM_013391.3	c.1194-996G>T		intron_variant	Intron 7 of 15	ENST00000255189.8	NP_037523.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000255189.8	c.1194-996G>T		intron_variant	Intron 7 of 15	1	NM_013391.3	ENSP00000255189.3
DMGDH	ENST00000523732.1	c.711-996G>T		intron_variant	Intron 4 of 11	1		ENSP00000430972.1
DMGDH	ENST00000517853.5	n.277-996G>T		intron_variant	Intron 2 of 9	2		ENSP00000428995.1
DMGDH	ENST00000518477.5	n.*428-996G>T		intron_variant	Intron 4 of 11	2		ENSP00000427834.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21316 AN: 151840 Hom.: 1836 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 21316 AN: 151958 Hom.: 1836 Cov.: 32 AF XY: 0.141 AC XY: 10457 AN XY: 74252

African (AFR) AF: 0.0537 AC: 2225 AN: 41464

American (AMR) AF: 0.174 AC: 2648 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3472

East Asian (EAS) AF: 0.0702 AC: 362 AN: 5156

South Asian (SAS) AF: 0.110 AC: 531 AN: 4806

European-Finnish (FIN) AF: 0.183 AC: 1925 AN: 10508

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12415 AN: 67976

Other (OTH) AF: 0.141 AC: 297 AN: 2110

Alfa AF: 0.101 Hom.: 228

Bravo AF: 0.136

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.52
PhyloP100		-0.016
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs248386; hg19: chr5-78330227;