NM_000868.4:c.551-13973T>C

Variant names:

• chrX-114892616-T-C
• rs10875535
• NM_000868.4:c.551-13973T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000868.4(HTR2C):​c.551-13973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 110,840 control chromosomes in the GnomAD database, including 72 homozygotes. There are 1,229 hemizygotes in GnomAD. 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 0.038 (72 hom., 1229 hem., cov: 23)
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

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.551-13973T>C		intron	N/A	NP_000859.2
	HTR2C	NM_001256760.3		c.551-13973T>C		intron	N/A	NP_001243689.2
	HTR2C	NM_001256761.3		c.456-13973T>C		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.551-13973T>C		intron	N/A	ENSP00000276198.1
	HTR2C	ENST00000371951.5	TSL:1	c.551-13973T>C		intron	N/A	ENSP00000361019.1
	HTR2C	ENST00000371950.3	TSL:1	c.456-13973T>C		intron	N/A	ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 4167 AN: 110810 Hom.: 72 Cov.: 23

Gnomad AFR AF: 0.00695

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.0409

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0376 AC: 4163 AN: 110840 Hom.: 72 Cov.: 23 AF XY: 0.0371 AC XY: 1229 AN XY: 33136

African (AFR) AF: 0.00694 AC: 213 AN: 30710

American (AMR) AF: 0.0275 AC: 285 AN: 10381

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 129 AN: 2649

East Asian (EAS) AF: 0.110 AC: 384 AN: 3479

South Asian (SAS) AF: 0.0914 AC: 243 AN: 2658

European-Finnish (FIN) AF: 0.0235 AC: 134 AN: 5704

Middle Eastern (MID) AF: 0.0455 AC: 9 AN: 198

European-Non Finnish (NFE) AF: 0.0508 AC: 2686 AN: 52874

Other (OTH) AF: 0.0452 AC: 68 AN: 1503

Alfa AF: 0.0425 Hom.: 1161

Bravo AF: 0.0370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		0.21
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: rs10875535; hg19: chrX-114127179;