rs7356530

Variant names:

• chr5-79105085-G-A
• rs7356530
• ENST00000520388.5:n.492-807C>T

Variant summary

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

The ENST00000520388.5(DMGDH):​n.492-807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,996 control chromosomes in the GnomAD database, including 22,507 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 0.52 (22507 hom., cov: 33)
• Consequence: DMGDH ENST00000520388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 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	ENST00000520388.5	n.492-807C>T		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79705 AN: 151878 Hom.: 22497 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.525 AC: 79751 AN: 151996 Hom.: 22507 Cov.: 33 AF XY: 0.527 AC XY: 39107 AN XY: 74260

African (AFR) AF: 0.302 AC: 12512 AN: 41468

American (AMR) AF: 0.595 AC: 9084 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1545 AN: 3466

East Asian (EAS) AF: 0.608 AC: 3145 AN: 5176

South Asian (SAS) AF: 0.518 AC: 2495 AN: 4818

European-Finnish (FIN) AF: 0.671 AC: 7082 AN: 10550

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41895 AN: 67932

Other (OTH) AF: 0.532 AC: 1123 AN: 2110

Alfa AF: 0.542 Hom.: 2980

Bravo AF: 0.509

Asia WGS AF: 0.540 AC: 1876 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.16
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs7356530; hg19: chr5-78400908;