Variant X-114731301-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_000868.4(HTR2C):c.43C>T(p.Leu15Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,180,022 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 2 hem. )

Consequence

HTR2C
NM_000868.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.25

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant X-114731301-C-T is Benign according to our data. Variant chrX-114731301-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3047470.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.24 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4 linkuse as main transcript	c.43C>T	p.Leu15Leu	synonymous_variant	4/6	ENST00000276198.6	NP_000859.2	P28335-1
HTR2C	NM_001256760.3 linkuse as main transcript	c.43C>T	p.Leu15Leu	synonymous_variant	5/7		NP_001243689.2	P28335-1
HTR2C	NM_001256761.3 linkuse as main transcript	c.43C>T	p.Leu15Leu	synonymous_variant	4/6		NP_001243690.2	P28335-2K9J958
LOC105373313	XR_001755943.2 linkuse as main transcript	n.574-525G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HTR2C	ENST00000276198.6 linkuse as main transcript	c.43C>T	p.Leu15Leu	synonymous_variant	4/6	1	NM_000868.4	ENSP00000276198.1	P28335-1
HTR2C	ENST00000371951.5 linkuse as main transcript	c.43C>T	p.Leu15Leu	synonymous_variant	5/7	1		ENSP00000361019.1	P28335-1
HTR2C	ENST00000371950.3 linkuse as main transcript	c.43C>T	p.Leu15Leu	synonymous_variant	4/6	1		ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes

AF:

0.000100

AC:

AN:

109716

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

32170

show subpopulations

Gnomad AFR

AF:

0.000332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000977

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:

0.00

GnomAD3 exomes

AF:

0.0000177

AC:

AN:

169476

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

57226

show subpopulations

Gnomad AFR exome

AF:

0.0000772

Gnomad AMR exome

AF:

0.0000405

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:

0.000244

GnomAD4 exome

AF:

0.00000374

AC:

AN:

1070306

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

341316

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000610

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:

0.00

Gnomad4 OTH exome

AF:

0.0000445

GnomAD4 genome

AF:

0.000100

AC:

AN:

109716

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

32170

show subpopulations

Gnomad4 AFR

AF:

0.000332

Gnomad4 AMR

AF:

0.0000977

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:

0.00

Bravo

AF:

0.0000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HTR2C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 09, 2022

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.2

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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