X-114849062-T-C

Position:

• chrX-114849062-T-C

Variant summary

Our verdict is Likely benign. Variant got -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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.550+859T>C		intron_variant		ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.550+859T>C		intron_variant			NP_001243689.2
HTR2C	NM_001256761.3	c.455+954T>C		intron_variant			NP_001243690.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.775 AC: 85696 AN: 110635 Hom.: 23906 Cov.: 23 AF XY: 0.783 AC XY: 25718 AN XY: 32855

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

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.821

Alfa AF: 0.833 Hom.: 42437

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4272555; hg19: chrX-114083625;