rs6318

Positions:

• chrX-114731326-C-G
• chrX-114731326-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

LOC105373313 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07872537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.68C>G	p.Ser23Cys	missense_variant	4/6	ENST00000276198.6	NP_000859.2
LOC105373313	XR_001755943.2	n.574-550G>C		intron_variant, non_coding_transcript_variant
HTR2C	NM_001256760.3	c.68C>G	p.Ser23Cys	missense_variant	5/7		NP_001243689.2
HTR2C	NM_001256761.3	c.68C>G	p.Ser23Cys	missense_variant	4/6		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.68C>G	p.Ser23Cys	missense_variant	4/6	1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371951.5	c.68C>G	p.Ser23Cys	missense_variant	5/7	1		ENSP00000361019	P1
HTR2C	ENST00000371950.3	c.68C>G	p.Ser23Cys	missense_variant	4/6	1		ENSP00000361018

Frequencies

GnomAD3 genomes AF: 0.794 AC: 85748 AN: 107951 Hom.: 24730 Cov.: 20 AF XY: 0.801 AC XY: 24288 AN XY: 30335

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

Gnomad4 AFR exome AF: 0.631

Gnomad4 AMR exome AF: 0.929

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.893

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.839

Gnomad4 OTH exome AF: 0.844

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

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.838

Alfa AF: 0.811 Hom.: 9079

Bravo AF: 0.788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6318; hg19: chrX-113965735;