rs1316753

Variant names:

• chr5-79235514-G-C
• rs1316753
• ENST00000518707.1:n.128+297C>G

Variant summary

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

The ENST00000518707.1(DMGDH):​n.128+297C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,124 control chromosomes in the GnomAD database, including 17,808 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 0.48 (17808 hom., cov: 33)
• Consequence: DMGDH ENST00000518707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

LOC124901011 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901011	XR_007058835.1	n.213+297C>G		intron_variant	Intron 1 of 1
LOC124901011	XR_007058836.1	n.213+297C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMGDH	ENST00000518707.1	n.128+297C>G		intron_variant	Intron 1 of 2	2
DMGDH	ENST00000520388.5	n.228+297C>G		intron_variant	Intron 1 of 4	4
DMGDH	ENST00000520855.1	n.195+297C>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72257 AN: 152008 Hom.: 17768 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.476 AC: 72359 AN: 152124 Hom.: 17808 Cov.: 33 AF XY: 0.480 AC XY: 35674 AN XY: 74354

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.463

Alfa AF: 0.434 Hom.: 1813

Bravo AF: 0.482

Asia WGS AF: 0.599 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.34
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1316753; hg19: chr5-78531337; COSMIC: COSV68660005;