rs558133

chr5-79129365-C-Achr5-79129365-C-T

Variant summary

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

The NM_001713.3(BHMT):c.1037+1382C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,088 control chromosomes in the GnomAD database, including 34,377 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 0.67 (34377 hom., cov: 32)
• Consequence: BHMT NM_001713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHMT	NM_001713.3	c.1037+1382C>A		intron_variant		ENST00000274353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHMT	ENST00000274353.10	c.1037+1382C>A		intron_variant		1	NM_001713.3	P1
BHMT	ENST00000524080.1	c.578+1382C>A		intron_variant		2
DMGDH	ENST00000518707.1	n.129-8013G>T		intron_variant, non_coding_transcript_variant		2
DMGDH	ENST00000520388.5	n.229-8013G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101351 AN: 151970 Hom.: 34352 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.667 AC: 101427 AN: 152088 Hom.: 34377 Cov.: 32 AF XY: 0.674 AC XY: 50087 AN XY: 74328

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.698

Alfa AF: 0.674 Hom.: 15948

Bravo AF: 0.670

Asia WGS AF: 0.816 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.2
Dann	Benign	0.28

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

Other links and lift over

dbSNP: rs558133; hg19: chr5-78425188;