rs6318

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-114731326-C-G
• chrX-114731326-C-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>G​(p.Ser23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 5/6 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: 𝑓 0.79 (24722 hom., 24325 hem., cov: 20)
  • Exomes 𝑓: 0.84 (260684 hom. 304330 hem.)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 252 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=0.07872537).

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>G	p.Ser23Cys	missense	Exon 4 of 6	NP_000859.2	P28335-1
	HTR2C	NM_001256760.3		c.68C>G	p.Ser23Cys	missense	Exon 5 of 7	NP_001243689.2	P28335-1
	HTR2C	NM_001256761.3		c.68C>G	p.Ser23Cys	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>G	p.Ser23Cys	missense	Exon 4 of 6	ENSP00000276198.1	P28335-1
	HTR2C	ENST00000371951.5	TSL:1	c.68C>G	p.Ser23Cys	missense	Exon 5 of 7	ENSP00000361019.1	P28335-1
	HTR2C	ENST00000371950.3	TSL:1	c.68C>G	p.Ser23Cys	missense	Exon 4 of 6	ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes AF: 0.794 AC: 85748 AN: 107951 Hom.: 24730 Cov.: 20

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.770

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.838

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.844 AC: 921798 AN: 1092460 Hom.: 260684 Cov.: 30 AF XY: 0.849 AC XY: 304330 AN XY: 358296

African (AFR) AF: 0.631 AC: 16554 AN: 26221

American (AMR) AF: 0.929 AC: 32514 AN: 35006

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 15132 AN: 19233

East Asian (EAS) AF: 0.983 AC: 29645 AN: 30166

South Asian (SAS) AF: 0.893 AC: 47973 AN: 53708

European-Finnish (FIN) AF: 0.879 AC: 35564 AN: 40478

Middle Eastern (MID) AF: 0.787 AC: 3232 AN: 4107

European-Non Finnish (NFE) AF: 0.839 AC: 702492 AN: 837696

Other (OTH) AF: 0.844 AC: 38692 AN: 45845

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.794 AC: 85770 AN: 107990 Hom.: 24722 Cov.: 20 AF XY: 0.801 AC XY: 24325 AN XY: 30384

African (AFR) AF: 0.638 AC: 18840 AN: 29543

American (AMR) AF: 0.896 AC: 8987 AN: 10033

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2047 AN: 2612

East Asian (EAS) AF: 0.988 AC: 3411 AN: 3453

South Asian (SAS) AF: 0.892 AC: 2158 AN: 2420

European-Finnish (FIN) AF: 0.885 AC: 4690 AN: 5300

Middle Eastern (MID) AF: 0.744 AC: 157 AN: 211

European-Non Finnish (NFE) AF: 0.836 AC: 43692 AN: 52272

Other (OTH) AF: 0.838 AC: 1229 AN: 1467

Alfa AF: 0.811 Hom.: 9079

Bravo AF: 0.788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
MetaRNN	Benign	0.079	T
PhyloP100		0.26
Sift4G	Benign	0.31	T
Vest4		0.14
gMVP		0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6318; hg19: chrX-113965735;