Variant 11-113944632-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006028.5(HTR3B):c.967T>G(p.Leu323Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,614,166 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 18 hom. )

Consequence

HTR3B
NM_006028.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.749

Variant links:

Genes affected

HTR3B (HGNC:5298): (5-hydroxytryptamine receptor 3B) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit B of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It is not functional as a homomeric complex, but a pentaheteromeric complex with subunit A (HTR3A) displays the full functional features of this receptor. [provided by RefSeq, Aug 2011]

HTR3B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069458187).

BP6

Variant 11-113944632-T-G is Benign according to our data. Variant chr11-113944632-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 777860.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3B	NM_006028.5 linkuse as main transcript	c.967T>G	p.Leu323Val	missense_variant	8/9	ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8 linkuse as main transcript	c.967T>G	p.Leu323Val	missense_variant	8/9	1	NM_006028.5	P2	O95264-1
HTR3B	ENST00000537778.5 linkuse as main transcript	c.934T>G	p.Leu312Val	missense_variant	7/8	1		A2	O95264-2
HTR3B	ENST00000543092.1 linkuse as main transcript	c.*15T>G		3_prime_UTR_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.00316

AC:

481

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00462

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00337

AC:

847

AN:

251450

Hom.:

AF XY:

0.00354

AC XY:

481

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00705

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00432

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00416

AC:

6085

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

3037

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00612

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00453

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00456

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.00316

AC:

481

AN:

152294

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

223

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00462

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00403

Hom.:

Bravo

AF:

0.00322

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00320

AC:

389

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00513

EpiControl

AF:

0.00456

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

Cadd

Benign

0.093

Dann

Benign

0.68

DEOGEN2

Benign

0.080

T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.0069

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-0.010

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.20

Sift

Benign

0.17

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.046

B;B

Vest4

0.16

MVP

0.43

MPC

0.19

ClinPred

0.012

GERP RS

-7.7

Varity_R

0.056

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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