rs3100725

Positions:

• chr2-137985596-G-A
• chr2-137985596-G-T

Variant summary

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

The NM_006895.3(HNMT):​c.191-15322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,926 control chromosomes in the GnomAD database, including 4,934 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 0.25 (4934 hom., cov: 32)
• Consequence: HNMT NM_006895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNMT	NM_006895.3	c.191-15322G>A		intron_variant		ENST00000280097.5
HNMT	XM_011511064.3	c.-188-15322G>A		intron_variant
HNMT	XM_017003948.2	c.89-15322G>A		intron_variant
HNMT	XM_017003949.3	c.191-15322G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNMT	ENST00000280097.5	c.191-15322G>A		intron_variant		1	NM_006895.3	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37755 AN: 151808 Hom.: 4926 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.249 AC: 37796 AN: 151926 Hom.: 4934 Cov.: 32 AF XY: 0.253 AC XY: 18778 AN XY: 74234

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.265

Alfa AF: 0.214 Hom.: 4935

Bravo AF: 0.252

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.4
DANN	Benign	0.41

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: rs3100725; hg19: chr2-138743166;