Variant rs6766410 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_130770.3(HTR3C):c.489C>A(p.Asn163Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,610,726 control chromosomes in the GnomAD database, including 151,190 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 14317 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136873 hom. )

Consequence

HTR3C
NM_130770.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.779

Variant links:

Genes affected

HTR3C (HGNC:24003): (5-hydroxytryptamine receptor 3C) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit C 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. Genes encoding subunits C, D and E form a cluster on chromosome 3. [provided by RefSeq, Jul 2008]

HTR3C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.896953E-6).

BP6

Variant 3-184056974-C-A is Benign according to our data. Variant chr3-184056974-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3C	NM_130770.3 linkuse as main transcript	c.489C>A	p.Asn163Lys	missense_variant	5/9	ENST00000318351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3C	ENST00000318351.2 linkuse as main transcript	c.489C>A	p.Asn163Lys	missense_variant	5/9	1	NM_130770.3	P1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65421

AN:

151830

Hom.:

14299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.409

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.453

AC:

113543

AN:

250782

Hom.:

26780

AF XY:

0.444

AC XY:

60131

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.459

Gnomad EAS exome

AF:

0.639

Gnomad SAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.430

AC:

627266

AN:

1458778

Hom.:

136873

Cov.:

AF XY:

0.427

AC XY:

309941

AN XY:

725708

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.453

Gnomad4 EAS exome

AF:

0.611

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.445

GnomAD4 genome

AF:

0.431

AC:

65470

AN:

151948

Hom.:

14317

Cov.:

AF XY:

0.435

AC XY:

32311

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.408

Gnomad4 AMR

AF:

0.467

Gnomad4 ASJ

AF:

0.455

Gnomad4 EAS

AF:

0.630

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.462

Gnomad4 NFE

AF:

0.421

Gnomad4 OTH

AF:

0.415

Alfa

AF:

0.419

Hom.:

22444

Bravo

AF:

0.435

TwinsUK

AF:

0.416

AC:

1543

ALSPAC

AF:

0.421

AC:

1622

ESP6500AA

AF:

0.416

AC:

1833

ESP6500EA

AF:

0.426

AC:

3661

ExAC

AF:

0.445

AC:

54066

Asia WGS

AF:

0.540

AC:

1878

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.057

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0000059

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.88

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.3

REVEL

Benign

0.12

Sift

Benign

0.056

Sift4G

Benign

0.19

Polyphen

0.044

Vest4

0.074

MutPred

0.21

Gain of methylation at N163 (P = 0.0057);

MPC

0.048

ClinPred

0.0064

GERP RS

0.97

Varity_R

0.13

gMVP

0.026

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over