X-114829460-G-T

Variant names:

• chrX-114829460-G-T
• rs6644093
• NM_000868.4:c.350-18543G>T

Variant summary

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

The NM_000868.4(HTR2C):​c.350-18543G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 106,774 control chromosomes in the GnomAD database, including 748 homozygotes. There are 3,955 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 0.12 (748 hom., 3955 hem., cov: 23)
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	NM_000868.4	MANE Select	c.350-18543G>T		intron	N/A	NP_000859.2	P28335-1
	HTR2C	NM_001256760.3		c.350-18543G>T		intron	N/A	NP_001243689.2	P28335-1
	HTR2C	NM_001256761.3		c.350-18543G>T		intron	N/A	NP_001243690.2	P28335-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2C	ENST00000276198.6	TSL:1 MANE Select	c.350-18543G>T		intron	N/A	ENSP00000276198.1	P28335-1
	HTR2C	ENST00000371951.5	TSL:1	c.350-18543G>T		intron	N/A	ENSP00000361019.1	P28335-1
	HTR2C	ENST00000371950.3	TSL:1	c.350-18543G>T		intron	N/A	ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes AF: 0.124 AC: 13189 AN: 106722 Hom.: 746 Cov.: 23

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0506

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.124 AC: 13196 AN: 106774 Hom.: 748 Cov.: 23 AF XY: 0.135 AC XY: 3955 AN XY: 29250

African (AFR) AF: 0.0244 AC: 724 AN: 29671

American (AMR) AF: 0.234 AC: 2268 AN: 9705

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 333 AN: 2564

East Asian (EAS) AF: 0.163 AC: 536 AN: 3293

South Asian (SAS) AF: 0.332 AC: 790 AN: 2380

European-Finnish (FIN) AF: 0.121 AC: 630 AN: 5220

Middle Eastern (MID) AF: 0.131 AC: 27 AN: 206

European-Non Finnish (NFE) AF: 0.148 AC: 7665 AN: 51620

Other (OTH) AF: 0.131 AC: 189 AN: 1443

Alfa AF: 0.135 Hom.: 3501

Bravo AF: 0.125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.6
DANN	Benign	0.88
PhyloP100		0.25
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6644093;

hg19: chrX-114064023;