X-114848165-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_000868.4(HTR2C):c.512C>T(p.Ala171Val) variant causes a missense change. The variant allele was found at a frequency of 0.000895 in 1,209,187 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 301 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00056 ( 0 hom., 14 hem., cov: 24)
Exomes 𝑓: 0.00093 ( 0 hom. 287 hem. )
Consequence
HTR2C
NM_000868.4 missense
NM_000868.4 missense
Scores
3
3
8
Clinical Significance
Conservation
PhyloP100: 6.01
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
Variant X-114848165-C-T is Benign according to our data. Variant chrX-114848165-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039474.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 14 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HTR2C | NM_000868.4 | c.512C>T | p.Ala171Val | missense_variant | 5/6 | ENST00000276198.6 | |
HTR2C | NM_001256760.3 | c.512C>T | p.Ala171Val | missense_variant | 6/7 | ||
HTR2C | NM_001256761.3 | c.455+57C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTR2C | ENST00000276198.6 | c.512C>T | p.Ala171Val | missense_variant | 5/6 | 1 | NM_000868.4 | P1 | |
HTR2C | ENST00000371951.5 | c.512C>T | p.Ala171Val | missense_variant | 6/7 | 1 | P1 | ||
HTR2C | ENST00000371950.3 | c.455+57C>T | intron_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.000561 AC: 63AN: 112335Hom.: 0 Cov.: 24 AF XY: 0.000405 AC XY: 14AN XY: 34527
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GnomAD3 exomes AF: 0.000544 AC: 99AN: 182029Hom.: 0 AF XY: 0.000615 AC XY: 41AN XY: 66655
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GnomAD4 exome AF: 0.000929 AC: 1019AN: 1096852Hom.: 0 Cov.: 30 AF XY: 0.000792 AC XY: 287AN XY: 362364
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GnomAD4 genome AF: 0.000561 AC: 63AN: 112335Hom.: 0 Cov.: 24 AF XY: 0.000405 AC XY: 14AN XY: 34527
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HTR2C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 25, 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). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Vest4
MVP
MPC
0.64
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at