rs955897

Variant names:

• chr5-79135663-A-C
• rs955897
• ENST00000518707.1:n.129-14311T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-79135663-A-C
• chr5-79135663-A-G
• chr5-79135663-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518707.1(DMGDH):​n.129-14311T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,832 control chromosomes in the GnomAD database, including 13,890 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 0.42 (13890 hom., cov: 32)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000518707.1	n.129-14311T>G		intron_variant	Intron 1 of 2	2
DMGDH	ENST00000520388.5	n.229-14311T>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64434 AN: 151712 Hom.: 13879 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.425 AC: 64492 AN: 151832 Hom.: 13890 Cov.: 32 AF XY: 0.433 AC XY: 32123 AN XY: 74198

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.439

Alfa AF: 0.179 Hom.: 313

Bravo AF: 0.424

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.9
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs955897; hg19: chr5-78431486;