X-114680518-G-C

Variant names:

• chrX-114680518-G-C
• rs12688102
• NM_000868.4:c.-79-46340G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.-79-46340G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (16563 hom., 21162 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 3 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

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.-79-46340G>C		intron	N/A	NP_000859.2	P28335-1
	HTR2C	NM_001256760.3		c.-170-37068G>C		intron	N/A	NP_001243689.2	P28335-1
	HTR2C	NM_001256761.3		c.-79-46340G>C		intron	N/A	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.-79-46340G>C		intron	N/A	ENSP00000276198.1	P28335-1
	HTR2C	ENST00000371951.5	TSL:1	c.-170-37068G>C		intron	N/A	ENSP00000361019.1	P28335-1
	HTR2C	ENST00000371950.3	TSL:1	c.-79-46340G>C		intron	N/A	ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes AF: 0.648 AC: 71592 AN: 110425 Hom.: 16571 Cov.: 23

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.701

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.648 AC: 71598 AN: 110476 Hom.: 16563 Cov.: 23 AF XY: 0.646 AC XY: 21162 AN XY: 32768

African (AFR) AF: 0.565 AC: 17170 AN: 30400

American (AMR) AF: 0.739 AC: 7677 AN: 10386

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 1696 AN: 2637

East Asian (EAS) AF: 0.852 AC: 2967 AN: 3483

South Asian (SAS) AF: 0.547 AC: 1430 AN: 2616

European-Finnish (FIN) AF: 0.725 AC: 4252 AN: 5861

Middle Eastern (MID) AF: 0.636 AC: 136 AN: 214

European-Non Finnish (NFE) AF: 0.658 AC: 34682 AN: 52698

Other (OTH) AF: 0.701 AC: 1053 AN: 1502

Alfa AF: 0.661 Hom.: 5177

Bravo AF: 0.653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs12688102; hg19: chrX-113914990;