rs1050900

Positions:

• chr2-138014348-A-T

Variant summary

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

The NM_006895.3(HNMT):​c.*218A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 423,498 control chromosomes in the GnomAD database, including 10,599 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 0.21 (3735 hom., cov: 32)
  • Exomes 𝑓: 0.22 (6864 hom.)
• Consequence: HNMT NM_006895.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

Genes affected

HNMT (HGNC:5028): (histamine N-methyltransferase) In mammals, histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative deamination via diamine oxidase. This gene encodes the first enzyme which is found in the cytosol and uses S-adenosyl-L-methionine as the methyl donor. In the mammalian brain, the neurotransmitter activity of histamine is controlled by N(tau)-methylation as diamine oxidase is not found in the central nervous system. A common genetic polymorphism affects the activity levels of this gene product in red blood cells. Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

LOC107985948 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNMT	NM_006895.3	c.*218A>T		3_prime_UTR_variant	6/6	ENST00000280097.5
LOC107985948	XR_001739719.2	n.239-6552T>A		intron_variant, non_coding_transcript_variant
HNMT	XM_011511064.3	c.*218A>T		3_prime_UTR_variant	5/5
HNMT	XM_017003948.2	c.*218A>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNMT	ENST00000280097.5	c.*218A>T		3_prime_UTR_variant	6/6	1	NM_006895.3	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32339 AN: 151912 Hom.: 3732 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.219 AC: 59385 AN: 271468 Hom.: 6864 Cov.: 0 AF XY: 0.221 AC XY: 30674 AN XY: 138720

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.265

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.213 AC: 32369 AN: 152030 Hom.: 3735 Cov.: 32 AF XY: 0.218 AC XY: 16161 AN XY: 74302

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.234

Alfa AF: 0.210 Hom.: 1975

Bravo AF: 0.212

Asia WGS AF: 0.330 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.90
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1050900; hg19: chr2-138771918;