2-138016068-C-T

Position:

• chr2-138016068-C-T

Variant summary

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

The NM_006895.3(HNMT):​c.*1938C>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 0.315 in 151,936 control chromosomes in the GnomAD database, including 9,005 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 0.31 (9005 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HNMT NM_006895.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNMT	NM_006895.3	c.*1938C>T		3_prime_UTR_variant	6/6	ENST00000280097.5
LOC107985948	XR_001739719.2	n.239-8272G>A		intron_variant, non_coding_transcript_variant
HNMT	XM_011511064.3	c.*1938C>T		3_prime_UTR_variant	5/5
HNMT	XM_017003948.2	c.*1938C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNMT	ENST00000280097.5	c.*1938C>T		3_prime_UTR_variant	6/6	1	NM_006895.3	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47713 AN: 151816 Hom.: 8982 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.312

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.315 AC: 47803 AN: 151936 Hom.: 9005 Cov.: 32 AF XY: 0.317 AC XY: 23540 AN XY: 74256

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.314

Alfa AF: 0.226 Hom.: 8570

Bravo AF: 0.329

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.65
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1455158; hg19: chr2-138773638;