Genetic Variant HRH3:p.Ala328Thr (chr20-62216362-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007232.3(HRH3):c.982G>A(p.Ala328Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A328S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

HRH3
NM_007232.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.00

Publications

0 publications found

Variant links:

Genes affected

HRH3 (HGNC:5184): (histamine receptor H3) Histamine is a ubiquitous messenger molecule released from mast cells, enterochromaffin-like cells, and neurons. Its various actions are mediated by histamine receptors H1, H2, H3 and H4. This gene encodes one of the histamine receptors (H3) which belongs to the family 1 of G protein-coupled receptors. It is an integral membrane protein and can regulate neurotransmitter release. This receptor can also increase voltage-dependent calcium current in smooth muscles and innervates the blood vessels and the heart in cardiovascular system. [provided by RefSeq, Jul 2008]

HRH3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08907294).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007232.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRH3	NM_007232.3	MANE Select	c.982G>A	p.Ala328Thr	missense	Exon 3 of 3	NP_009163.2	Q9Y5N1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HRH3	ENST00000340177.10	TSL:1 MANE Select	c.982G>A	p.Ala328Thr	missense	Exon 3 of 3	ENSP00000342560.5	Q9Y5N1-1
HRH3	ENST00000317393.10	TSL:1	c.822-80G>A		intron	N/A	ENSP00000321482.7	A0A0A0MR48
HRH3	ENST00000932927.1		c.940G>A	p.Ala314Thr	missense	Exon 3 of 3	ENSP00000602986.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1425350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32644

American (AMR)

AF:

0.00

AC:

AN:

39892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25496

East Asian (EAS)

AF:

0.00

AC:

AN:

37470

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093256

Other (OTH)

AF:

0.00

AC:

AN:

58900

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.093

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.68

M_CAP

Benign

0.015

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.96

PhyloP100

2.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.90

REVEL

Benign

0.071

Sift

Benign

0.32

Sift4G

Benign

0.46

Polyphen

0.018

Vest4

0.16

MutPred

0.30

Gain of phosphorylation at A328 (P = 0.0062)

MVP

0.83

MPC

0.40

ClinPred

0.098

GERP RS

3.6

Varity_R

0.066

gMVP

0.79

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over