rs3100719

chr2-138006364-G-A

Variant summary

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

The NM_006895.3(HNMT):c.523+1139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,660 control chromosomes in the GnomAD database, including 4,314 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 0.23 (4314 hom., cov: 32)
• Consequence: HNMT NM_006895.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNMT	NM_006895.3	c.523+1139G>A		intron_variant		ENST00000280097.5
LOC107985948	XR_001739719.2	n.1671C>T		non_coding_transcript_exon_variant	3/3
HNMT	XM_011511064.3	c.145+1139G>A		intron_variant
HNMT	XM_017003948.2	c.421+1139G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNMT	ENST00000280097.5	c.523+1139G>A		intron_variant		1	NM_006895.3	P1
HNMT	ENST00000410115.5	c.523+1139G>A		intron_variant		5		P1
HNMT	ENST00000485653.1	n.455+1139G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35215 AN: 151542 Hom.: 4311 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.232 AC: 35253 AN: 151660 Hom.: 4314 Cov.: 32 AF XY: 0.237 AC XY: 17554 AN XY: 74122

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.245

Alfa AF: 0.226 Hom.: 485

Bravo AF: 0.233

Asia WGS AF: 0.329 AC: 1142 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.6
Dann	Benign	0.72

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: rs3100719; hg19: chr2-138763934; COSMIC: COSV54507459; COSMIC: COSV54507459;