X-114657295-A-G

Variant names:

• chrX-114657295-A-G
• rs2192372
• NM_000868.4:c.-80+43414A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.-80+43414A>G 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 (16837 hom., 20887 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 8 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.-80+43414A>G		intron	N/A	NP_000859.2	P28335-1
	HTR2C	NM_001256760.3		c.-171+43414A>G		intron	N/A	NP_001243689.2	P28335-1
	HTR2C	NM_001256761.3		c.-80+43414A>G		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.-80+43414A>G		intron	N/A	ENSP00000276198.1	P28335-1
	HTR2C	ENST00000371951.5	TSL:1	c.-171+43414A>G		intron	N/A	ENSP00000361019.1	P28335-1
	HTR2C	ENST00000371950.3	TSL:1	c.-80+43414A>G		intron	N/A	ENSP00000361018.3	P28335-2

Frequencies

GnomAD3 genomes AF: 0.655 AC: 71668 AN: 109371 Hom.: 16847 Cov.: 22

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.702

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: 0.655 AC: 71683 AN: 109420 Hom.: 16837 Cov.: 22 AF XY: 0.654 AC XY: 20887 AN XY: 31924

African (AFR) AF: 0.580 AC: 17562 AN: 30295

American (AMR) AF: 0.742 AC: 7553 AN: 10173

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 1662 AN: 2609

East Asian (EAS) AF: 0.851 AC: 2968 AN: 3489

South Asian (SAS) AF: 0.557 AC: 1455 AN: 2612

European-Finnish (FIN) AF: 0.733 AC: 4149 AN: 5657

Middle Eastern (MID) AF: 0.638 AC: 134 AN: 210

European-Non Finnish (NFE) AF: 0.663 AC: 34635 AN: 52232

Other (OTH) AF: 0.702 AC: 1030 AN: 1467

Alfa AF: 0.658 Hom.: 4942

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.040

Splicing

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: rs2192372; hg19: chrX-113891773;