X-114849062-T-C

Variant names:

• chrX-114849062-T-C
• rs4272555
• NM_000868.4:c.550+859T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000868.4(HTR2C):​c.550+859T>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 0.77 (23894 hom., 25737 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 9 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.550+859T>C		intron_variant	Intron 5 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.550+859T>C		intron_variant	Intron 6 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.455+954T>C		intron_variant	Intron 5 of 5		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.550+859T>C		intron_variant	Intron 5 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.550+859T>C		intron_variant	Intron 6 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.455+954T>C		intron_variant	Intron 5 of 5	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.775 AC: 85696 AN: 110635 Hom.: 23906 Cov.: 23

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.821

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: 0.774 AC: 85695 AN: 110687 Hom.: 23894 Cov.: 23 AF XY: 0.782 AC XY: 25737 AN XY: 32917

African (AFR) AF: 0.552 AC: 16844 AN: 30497

American (AMR) AF: 0.888 AC: 9196 AN: 10357

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2143 AN: 2634

East Asian (EAS) AF: 0.990 AC: 3490 AN: 3527

South Asian (SAS) AF: 0.893 AC: 2334 AN: 2615

European-Finnish (FIN) AF: 0.883 AC: 5131 AN: 5809

Middle Eastern (MID) AF: 0.781 AC: 164 AN: 210

European-Non Finnish (NFE) AF: 0.844 AC: 44606 AN: 52855

Other (OTH) AF: 0.821 AC: 1233 AN: 1502

Alfa AF: 0.800 Hom.: 53507

Bravo AF: 0.766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.6
DANN	Benign	0.95
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs4272555; hg19: chrX-114083625;