2-138002079-C-T

Position:

chr2-138002079-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006895.3(HNMT):c.314C>T(p.Thr105Ile) variant causes a missense change. The variant allele was found at a frequency of 0.103 in 1,585,920 control chromosomes in the GnomAD database, including 9,188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

Frequency

Genomes: 𝑓 0.084 ( 732 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8456 hom. )

Consequence

HNMT
NM_006895.3 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: 5.03

Variant links:

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]

HNMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016437471).

BP6

Variant 2-138002079-C-T is Benign according to our data. Variant chr2-138002079-C-T is described in ClinVar as [Benign, risk_factor]. Clinvar id is 5160.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HNMT	NM_006895.3 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	4/6	ENST00000280097.5
HNMT	XM_017003948.2 linkuse as main transcript	c.212C>T	p.Thr71Ile	missense_variant	4/6
HNMT	XM_017003949.3 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	4/5
HNMT	XM_011511064.3 linkuse as main transcript	c.-65C>T		5_prime_UTR_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNMT	ENST00000280097.5 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	4/6	1	NM_006895.3	P1	P50135-1
HNMT	ENST00000410115.5 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	5/7	5		P1	P50135-1
HNMT	ENST00000467390.5 linkuse as main transcript	n.326C>T		non_coding_transcript_exon_variant	4/5	2
HNMT	ENST00000485653.1 linkuse as main transcript	n.246C>T		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.0844

AC:

12821

AN:

151994

Hom.:

731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.0868

Gnomad ASJ

AF:

0.0812

Gnomad EAS

AF:

0.0342

Gnomad SAS

AF:

0.0956

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0848

GnomAD3 exomes

AF:

0.0998

AC:

23502

AN:

235484

Hom.:

1396

AF XY:

0.102

AC XY:

12922

AN XY:

127296

show subpopulations

Gnomad AFR exome

AF:

0.0167

Gnomad AMR exome

AF:

0.0972

Gnomad ASJ exome

AF:

0.0711

Gnomad EAS exome

AF:

0.0379

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.105

AC:

150234

AN:

1433808

Hom.:

8456

Cov.:

AF XY:

0.105

AC XY:

74795

AN XY:

712614

show subpopulations

Gnomad4 AFR exome

AF:

0.0160

Gnomad4 AMR exome

AF:

0.0946

Gnomad4 ASJ exome

AF:

0.0758

Gnomad4 EAS exome

AF:

0.0459

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.0969

GnomAD4 genome

AF:

0.0843

AC:

12824

AN:

152112

Hom.:

732

Cov.:

AF XY:

0.0863

AC XY:

6414

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0197

Gnomad4 AMR

AF:

0.0868

Gnomad4 ASJ

AF:

0.0812

Gnomad4 EAS

AF:

0.0341

Gnomad4 SAS

AF:

0.0957

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.0853

Alfa

AF:

0.101

Hom.:

1022

Bravo

AF:

0.0733

TwinsUK

AF:

0.109

AC:

403

ALSPAC

AF:

0.103

AC:

397

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.105

AC:

901

ExAC

AF:

0.101

AC:

12228

Asia WGS

AF:

0.0800

AC:

276

AN:

3478

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HNMT-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inherited susceptibility to asthma

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

.;D

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.089

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.73

P;P

Vest4

0.11

MPC

0.27

ClinPred

0.044

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.38

gMVP

0.54

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over