X-114638137-T-C

Position:

• chrX-114638137-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.-80+24256T>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 0.66 (16980 hom., 21426 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2C	NM_000868.4	c.-80+24256T>C		intron_variant		ENST00000276198.6
HTR2C	NM_001256760.3	c.-171+24256T>C		intron_variant
HTR2C	NM_001256761.3	c.-80+24256T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2C	ENST00000276198.6	c.-80+24256T>C		intron_variant		1	NM_000868.4	P1
HTR2C	ENST00000371950.3	c.-80+24256T>C		intron_variant		1
HTR2C	ENST00000371951.5	c.-171+24256T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 72528 AN: 110468 Hom.: 16988 Cov.: 23 AF XY: 0.654 AC XY: 21399 AN XY: 32704

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.703

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: 0.656 AC: 72545 AN: 110523 Hom.: 16980 Cov.: 23 AF XY: 0.654 AC XY: 21426 AN XY: 32769

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.703

Alfa AF: 0.660 Hom.: 7919

Bravo AF: 0.662

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9698290; hg19: chrX-113872608;