rs6877474

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000255189.8(DMGDH):​c.101+536A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 152,358 control chromosomes in the GnomAD database, including 10 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 0.0076 ( 10 hom., cov: 33)

Consequence

DMGDH
ENST00000255189.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00759 (1157/152358) while in subpopulation AFR AF= 0.0261 (1085/41574). AF 95% confidence interval is 0.0248. There are 10 homozygotes in gnomad4. There are 548 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DMGDHNM_013391.3 linkuse as main transcriptc.101+536A>C intron_variant ENST00000255189.8 NP_037523.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DMGDHENST00000255189.8 linkuse as main transcriptc.101+536A>C intron_variant 1 NM_013391.3 ENSP00000255189 P1Q9UI17-1

Frequencies

GnomAD3 genomes
AF:
0.00756
AC:
1151
AN:
152240
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0260
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00621
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00759
AC:
1157
AN:
152358
Hom.:
10
Cov.:
33
AF XY:
0.00736
AC XY:
548
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.0261
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00615
Alfa
AF:
0.00385
Hom.:
4
Bravo
AF:
0.00848
Asia WGS
AF:
0.00635
AC:
22
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.74
DANN
Benign
0.58

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6877474; hg19: chr5-78364807; API