chrX-114731326-C-T

Variant names:

• chrX-114731326-C-T
• rs6318
• NM_000868.4:c.68C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000868.4(HTR2C):​c.68C>T​(p.Ser23Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 251 publications found

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]

ENSG00000306059 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07866609).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000868.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	NM_000868.4	MANE Select	c.68C>T	p.Ser23Phe	missense	Exon 4 of 6	NP_000859.2	P28335-1
	HTR2C	NM_001256760.3		c.68C>T	p.Ser23Phe	missense	Exon 5 of 7	NP_001243689.2	P28335-1
	HTR2C	NM_001256761.3		c.68C>T	p.Ser23Phe	missense	Exon 4 of 6	NP_001243690.2	P28335-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	ENST00000276198.6	TSL:1 MANE Select	c.68C>T	p.Ser23Phe	missense	Exon 4 of 6	ENSP00000276198.1	P28335-1
	HTR2C	ENST00000371951.5	TSL:1	c.68C>T	p.Ser23Phe	missense	Exon 5 of 7	ENSP00000361019.1	P28335-1
	HTR2C	ENST00000371950.3	TSL:1	c.68C>T	p.Ser23Phe	missense	Exon 4 of 6	ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1092530 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 358320

African (AFR) AF: 0.00 AC: 0 AN: 26221

American (AMR) AF: 0.00 AC: 0 AN: 35009

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19235

East Asian (EAS) AF: 0.00 AC: 0 AN: 30164

South Asian (SAS) AF: 0.00 AC: 0 AN: 53711

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4107

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837753

Other (OTH) AF: 0.00 AC: 0 AN: 45850

GnomAD4 genome Cov.: 20

Alfa AF: 0.00 Hom.: 9079

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
MetaRNN	Benign	0.079	T
PhyloP100		0.26
Sift4G	Benign	0.74	T
Vest4		0.11
gMVP		0.50

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

Other links and lift over

dbSNP: rs6318; hg19: chrX-113965735;