11-113975319-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000375498.6(HTR3A):c.12G>T(p.Lys4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000744 in 1,613,458 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00072 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 16 hom. )

Consequence

HTR3A
ENST00000375498.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.898

Variant links:

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A 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 appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

HTR3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039993823).

BP6

Variant 11-113975319-G-T is Benign according to our data. Variant chr11-113975319-G-T is described in ClinVar as [Benign]. Clinvar id is 732221.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000722 (110/152356) while in subpopulation EAS AF= 0.0185 (96/5178). AF 95% confidence interval is 0.0155. There are 1 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
HTR3A	NM_000869.6 linkuse as main transcript	c.-7G>T	5_prime_UTR_variant	1/9	ENST00000504030.7
HTR3A	NM_213621.4 linkuse as main transcript	c.-7G>T	5_prime_UTR_variant	1/8
HTR3A	NR_046363.2 linkuse as main transcript	n.212G>T	non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7 linkuse as main transcript	c.-7G>T		5_prime_UTR_variant	1/9	1	NM_000869.6	P1	P46098-1

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

111

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00165

AC:

412

AN:

249970

Hom.:

AF XY:

0.00158

AC XY:

214

AN XY:

135180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0206

Gnomad SAS exome

AF:

0.000753

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000747

AC:

1091

AN:

1461102

Hom.:

Cov.:

AF XY:

0.000762

AC XY:

554

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0236

Gnomad4 SAS exome

AF:

0.000940

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000722

AC:

110

AN:

152356

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0185

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000467

Hom.:

Bravo

AF:

0.00101

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00180

AC:

219

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.40

T;T

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.13

Sift

Benign

0.14

T;T

Sift4G

Benign

0.12

T;T

Vest4

0.29

MutPred

0.38

Loss of MoRF binding (P = 0.0145);Loss of MoRF binding (P = 0.0145);

MVP

0.82

MPC

0.092

ClinPred

0.043

GERP RS

2.8

gMVP

0.76

Splicing

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