rs567754

Variant names:

• chr5-79120593-C-A
• rs567754
• NM_001713.3:c.477+52C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-79120593-C-A
• chr5-79120593-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001713.3(BHMT):​c.477+52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 39 publications found

Genes affected

BHMT (HGNC:1047): (betaine--homocysteine S-methyltransferase) This gene encodes a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. Defects in this gene could lead to hyperhomocyst(e)inemia, but such a defect has not yet been observed. [provided by RefSeq, Jul 2008]

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BHMT	NM_001713.3	c.477+52C>A		intron_variant	Intron 4 of 7	ENST00000274353.10	NP_001704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BHMT	ENST00000274353.10	c.477+52C>A		intron_variant	Intron 4 of 7	1	NM_001713.3	ENSP00000274353.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1355910 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 668224

African (AFR) AF: 0.00 AC: 0 AN: 30000

American (AMR) AF: 0.00 AC: 0 AN: 31068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21440

East Asian (EAS) AF: 0.00 AC: 0 AN: 37702

South Asian (SAS) AF: 0.00 AC: 0 AN: 68686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3860

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056704

Other (OTH) AF: 0.00 AC: 0 AN: 55918

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 15238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		-0.40

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: rs567754; hg19: chr5-78416416;