chrX-114731382-G-C

Position:

chrX-114731382-G-C

Variant summary

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

The NM_000868.4(HTR2C):c.124G>C(p.Asp42His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,202,185 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 51 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., 23 hem., cov: 22)

Exomes 𝑓: 0.000090 ( 0 hom. 28 hem. )

Consequence

HTR2C
NM_000868.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

HTR2C (HGNC:5295): (5-hydroxytryptamine receptor 2C) This gene encodes a seven-transmembrane G-protein-coupled receptor. The encoded protein responds to signaling through the neurotransmitter serotonin. The mRNA of this gene is subject to multiple RNA editing events, where adenosine residues encoded by the genome are converted to inosines. RNA editing is predicted to alter the structure of the second intracellular loop, thereby generating alternate protein forms with decreased ability to interact with G proteins. Abnormalities in RNA editing of this gene have been detected in victims of suicide that suffer from depression. In addition, naturally-occuring variation in the promoter and 5' non-coding and coding regions of this gene may show statistically-significant association with mental illness and behavioral disorders. Alternative splicing results in multiple different transcript variants. [provided by RefSeq, Jan 2015]

HTR2C links:

LOC105373313 (HGNC:):

LOC105373313 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010652423).

BP6

Variant X-114731382-G-C is Benign according to our data. Variant chrX-114731382-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 738592.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4 linkuse as main transcript	c.124G>C	p.Asp42His	missense_variant	4/6	ENST00000276198.6	NP_000859.2	P28335-1
HTR2C	NM_001256760.3 linkuse as main transcript	c.124G>C	p.Asp42His	missense_variant	5/7		NP_001243689.2	P28335-1
HTR2C	NM_001256761.3 linkuse as main transcript	c.124G>C	p.Asp42His	missense_variant	4/6		NP_001243690.2	P28335-2K9J958
LOC105373313	XR_001755943.2 linkuse as main transcript	n.574-606C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HTR2C	ENST00000276198.6 linkuse as main transcript	c.124G>C	p.Asp42His	missense_variant	4/6	1	NM_000868.4	ENSP00000276198.1	P28335-1
HTR2C	ENST00000371951.5 linkuse as main transcript	c.124G>C	p.Asp42His	missense_variant	5/7	1		ENSP00000361019.1	P28335-1
HTR2C	ENST00000371950.3 linkuse as main transcript	c.124G>C	p.Asp42His	missense_variant	4/6	1		ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes

AF:

0.000742

AC:

AN:

110499

Hom.:

Cov.:

AF XY:

0.000702

AC XY:

AN XY:

32781

show subpopulations

Gnomad AFR

AF:

0.00254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000292

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.000229

AC:

AN:

183396

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

67838

show subpopulations

Gnomad AFR exome

AF:

0.00304

Gnomad AMR exome

AF:

0.0000730

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000898

AC:

AN:

1091641

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

357139

show subpopulations

Gnomad4 AFR exome

AF:

0.00358

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000742

AC:

AN:

110544

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

AN XY:

32836

show subpopulations

Gnomad4 AFR

AF:

0.00253

Gnomad4 AMR

AF:

0.000292

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00134

Alfa

AF:

0.0000678

Hom.:

Bravo

AF:

0.000774

ESP6500AA

AF:

0.00209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HTR2C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 13, 2021

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Uncertain

0.94

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.57

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.073

T;T;D

Sift4G

Uncertain

0.059

T;T;D

Vest4

0.11

MVP

0.64

MPC

0.44

ClinPred

0.048

GERP RS

3.3

gMVP

0.31

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