chrX-114731461-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000868.4(HTR2C):āc.203T>Cā(p.Ile68Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,011 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 23)
Exomes š: 0.0000027 ( 0 hom. 2 hem. )
Consequence
HTR2C
NM_000868.4 missense
NM_000868.4 missense
Scores
1
7
6
Clinical Significance
Conservation
PhyloP100: 8.02
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 -4 ACMG points.
BS2
High Hemizygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HTR2C | NM_000868.4 | c.203T>C | p.Ile68Thr | missense_variant | 4/6 | ENST00000276198.6 | |
LOC105373313 | XR_001755943.2 | n.574-685A>G | intron_variant, non_coding_transcript_variant | ||||
HTR2C | NM_001256760.3 | c.203T>C | p.Ile68Thr | missense_variant | 5/7 | ||
HTR2C | NM_001256761.3 | c.203T>C | p.Ile68Thr | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTR2C | ENST00000276198.6 | c.203T>C | p.Ile68Thr | missense_variant | 4/6 | 1 | NM_000868.4 | P1 | |
HTR2C | ENST00000371951.5 | c.203T>C | p.Ile68Thr | missense_variant | 5/7 | 1 | P1 | ||
HTR2C | ENST00000371950.3 | c.203T>C | p.Ile68Thr | missense_variant | 4/6 | 1 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome AF: 0.00000273 AC: 3AN: 1097011Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 2AN XY: 362377
GnomAD4 exome
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3
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1097011
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31
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2
AN XY:
362377
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2023 | The c.203T>C (p.I68T) alteration is located in exon 4 (coding exon 2) of the HTR2C gene. This alteration results from a T to C substitution at nucleotide position 203, causing the isoleucine (I) at amino acid position 68 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Vest4
MutPred
Loss of stability (P = 0.0436);Loss of stability (P = 0.0436);Loss of stability (P = 0.0436);
MVP
MPC
1.3
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at