chr5-79090022-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017614.5(BHMT2):​c.*1448T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,132 control chromosomes in the GnomAD database, including 15,120 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 0.41 ( 15120 hom., cov: 32)

Consequence

BHMT2
NM_017614.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.565
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BHMT2NM_017614.5 linkc.*1448T>G 3_prime_UTR_variant 8/8 ENST00000255192.8 NP_060084.2 Q9H2M3-1A0A024RAQ0
BHMT2NM_001178005.2 linkc.*1448T>G 3_prime_UTR_variant 7/7 NP_001171476.1 Q9H2M3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BHMT2ENST00000255192.8 linkc.*1448T>G 3_prime_UTR_variant 8/81 NM_017614.5 ENSP00000255192.3 Q9H2M3-1
DMGDHENST00000520388.5 linkn.606+14142A>C intron_variant 4

Frequencies

GnomAD3 genomes
AF:
0.406
AC:
61647
AN:
152014
Hom.:
15114
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.113
Gnomad AMI
AF:
0.692
Gnomad AMR
AF:
0.521
Gnomad ASJ
AF:
0.379
Gnomad EAS
AF:
0.611
Gnomad SAS
AF:
0.454
Gnomad FIN
AF:
0.577
Gnomad MID
AF:
0.456
Gnomad NFE
AF:
0.508
Gnomad OTH
AF:
0.432
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.405
AC:
61654
AN:
152132
Hom.:
15120
Cov.:
32
AF XY:
0.410
AC XY:
30521
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.113
Gnomad4 AMR
AF:
0.522
Gnomad4 ASJ
AF:
0.379
Gnomad4 EAS
AF:
0.610
Gnomad4 SAS
AF:
0.456
Gnomad4 FIN
AF:
0.577
Gnomad4 NFE
AF:
0.508
Gnomad4 OTH
AF:
0.430
Alfa
AF:
0.446
Hom.:
3508
Bravo
AF:
0.390
Asia WGS
AF:
0.503
AC:
1750
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
2.5
DANN
Benign
0.72

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10944; hg19: chr5-78385845; API