rs585800

chr5-79131385-T-A

Variant summary

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

The NM_001713.3(BHMT):c.*269T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 319,430 control chromosomes in the GnomAD database, including 100,039 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 0.81 (50864 hom., cov: 32)
  • Exomes 𝑓: 0.76 (49175 hom.)
• Consequence: BHMT NM_001713.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BHMT	NM_001713.3	c.*269T>A		3_prime_UTR_variant	8/8	ENST00000274353.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BHMT	ENST00000274353.10	c.*269T>A		3_prime_UTR_variant	8/8	1	NM_001713.3	P1
BHMT	ENST00000524080.1	c.*269T>A		3_prime_UTR_variant	5/5	2
DMGDH	ENST00000518707.1	n.129-10033A>T		intron_variant, non_coding_transcript_variant		2
DMGDH	ENST00000520388.5	n.229-10033A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123228 AN: 152056 Hom.: 50798 Cov.: 32

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.830

GnomAD4 exome AF: 0.763 AC: 127595 AN: 167254 Hom.: 49175 Cov.: 3 AF XY: 0.765 AC XY: 66530 AN XY: 86940

Gnomad4 AFR exome AF: 0.950

Gnomad4 AMR exome AF: 0.856

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 0.882

Gnomad4 SAS exome AF: 0.867

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.811 AC: 123355 AN: 152176 Hom.: 50864 Cov.: 32 AF XY: 0.813 AC XY: 60510 AN XY: 74398

Gnomad4 AFR AF: 0.953

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.848

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.831

Alfa AF: 0.756 Hom.: 5494

Bravo AF: 0.830

Asia WGS AF: 0.903 AC: 3139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.1
Dann	Benign	0.65

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: rs585800; hg19: chr5-78427208;