5-79083001-C-T

Position:

• chr5-79083001-C-T

Variant summary

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

The ENST00000255192.8(BHMT2):​c.598+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 1,608,400 control chromosomes in the GnomAD database, including 7,323 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 0.070 (507 hom., cov: 32)
  • Exomes 𝑓: 0.093 (6816 hom.)
• Consequence: BHMT2 ENST00000255192.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

BHMT2 (HGNC:1048): (betaine--homocysteine S-methyltransferase 2) Homocysteine is a sulfur-containing amino acid that plays a crucial role in methylation reactions. Transfer of the methyl group from betaine to homocysteine creates methionine, which donates the methyl group to methylate DNA, proteins, lipids, and other intracellular metabolites. The protein encoded by this gene is one of two methyl transferases that can catalyze the transfer of the methyl group from betaine to homocysteine. Anomalies in homocysteine metabolism have been implicated in disorders ranging from vascular disease to neural tube birth defects such as spina bifida. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BHMT2	NM_017614.5	c.598+45C>T		intron_variant		ENST00000255192.8	NP_060084.2
BHMT2	NM_001178005.2	c.406+45C>T		intron_variant			NP_001171476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BHMT2	ENST00000255192.8	c.598+45C>T		intron_variant		1	NM_017614.5	ENSP00000255192	P1

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10586 AN: 151856 Hom.: 508 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0655

GnomAD3 exomes AF: 0.0725 AC: 18050 AN: 248924 Hom.: 797 AF XY: 0.0740 AC XY: 9955 AN XY: 134484

Gnomad AFR exome AF: 0.0184

Gnomad AMR exome AF: 0.0415

Gnomad ASJ exome AF: 0.0626

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.0534

Gnomad FIN exome AF: 0.0892

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0809

GnomAD4 exome AF: 0.0933 AC: 135854 AN: 1456426 Hom.: 6816 Cov.: 30 AF XY: 0.0924 AC XY: 66926 AN XY: 724080

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.0430

Gnomad4 ASJ exome AF: 0.0652

Gnomad4 EAS exome AF: 0.000303

Gnomad4 SAS exome AF: 0.0536

Gnomad4 FIN exome AF: 0.0900

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0783

GnomAD4 genome AF: 0.0697 AC: 10586 AN: 151974 Hom.: 507 Cov.: 32 AF XY: 0.0690 AC XY: 5127 AN XY: 74268

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.0532

Gnomad4 ASJ AF: 0.0632

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0941

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0893 Hom.: 180

Bravo AF: 0.0632

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.68

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: rs41272270; hg19: chr5-78378824;