X-114585887-C-T

Variant names:

• chrX-114585887-C-T
• rs569959
• NM_000868.4:c.-147+1228C>T

Variant summary

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

The NM_000868.4(HTR2C):​c.-147+1228C>T 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 (16922 hom., 18895 hem., cov: 20)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407
• Publications: 10 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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-147+1228C>T		intron_variant	Intron 1 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-238+1228C>T		intron_variant	Intron 1 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.-147+1228C>T		intron_variant	Intron 1 of 5		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-147+1228C>T		intron_variant	Intron 1 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.-238+1228C>T		intron_variant	Intron 1 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.-147+1228C>T		intron_variant	Intron 1 of 5	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 69899 AN: 106740 Hom.: 16933 Cov.: 20

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.689

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: 0.655 AC: 69901 AN: 106788 Hom.: 16922 Cov.: 20 AF XY: 0.645 AC XY: 18895 AN XY: 29314

African (AFR) AF: 0.622 AC: 18205 AN: 29253

American (AMR) AF: 0.649 AC: 6411 AN: 9876

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 1651 AN: 2590

East Asian (EAS) AF: 0.846 AC: 2806 AN: 3317

South Asian (SAS) AF: 0.587 AC: 1369 AN: 2333

European-Finnish (FIN) AF: 0.713 AC: 3715 AN: 5208

Middle Eastern (MID) AF: 0.647 AC: 134 AN: 207

European-Non Finnish (NFE) AF: 0.657 AC: 34099 AN: 51911

Other (OTH) AF: 0.690 AC: 984 AN: 1426

Alfa AF: 0.651 Hom.: 4868

Bravo AF: 0.653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs569959; hg19: chrX-113820360;