chrX-114878807-A-T

Variant names:

• chrX-114878807-A-T
• rs5946018
• NM_000868.4:c.551-27782A>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.551-27782A>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 0.0 (0 hom., 0 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• Publications: 2 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=-0.99).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	NM_000868.4	MANE Select	c.551-27782A>T		intron	N/A	NP_000859.2
	HTR2C	NM_001256760.3		c.551-27782A>T		intron	N/A	NP_001243689.2
	HTR2C	NM_001256761.3		c.456-27782A>T		intron	N/A	NP_001243690.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	ENST00000276198.6	TSL:1 MANE Select	c.551-27782A>T		intron	N/A	ENSP00000276198.1
	HTR2C	ENST00000371951.5	TSL:1	c.551-27782A>T		intron	N/A	ENSP00000361019.1
	HTR2C	ENST00000371950.3	TSL:1	c.456-27782A>T		intron	N/A	ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 109106 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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: AC0 AF: 0.00 AC: 0 AN: 109106 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 31674

African (AFR) AF: 0.00 AC: 0 AN: 30199

American (AMR) AF: 0.00 AC: 0 AN: 10109

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2615

East Asian (EAS) AF: 0.00 AC: 0 AN: 3503

South Asian (SAS) AF: 0.00 AC: 0 AN: 2630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5581

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52102

Other (OTH) AF: 0.00 AC: 0 AN: 1470

Alfa AF: 0.000258 Hom.: 2753

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		-0.66

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: rs5946018; hg19: chrX-114113370;