X-114584109-C-G

Position:

• chrX-114584109-C-G

Variant summary

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

The NM_000868.4(HTR2C):​c.-697C>G variant causes a 5 prime UTR 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 (17035 hom., 21550 hem., cov: 23)
  • Exomes 𝑓: 0.73 (52 hom. 100 hem.)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-697C>G		5_prime_UTR_variant	1/6	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-788C>G		5_prime_UTR_variant	1/7		NP_001243689.2
HTR2C	NM_001256761.3	c.-697C>G		5_prime_UTR_variant	1/6		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-697C>G		5_prime_UTR_variant	1/6	1	NM_000868.4	ENSP00000276198	P1
HTR2C	ENST00000371950.3	c.-697C>G		5_prime_UTR_variant	1/6	1		ENSP00000361018
HTR2C	ENST00000371951.5	c.-788C>G		5_prime_UTR_variant	1/7	1		ENSP00000361019	P1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 72811 AN: 110478 Hom.: 17046 Cov.: 23 AF XY: 0.658 AC XY: 21531 AN XY: 32718

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.660

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.691

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.729 AC: 239 AN: 328 Hom.: 52 Cov.: 0 AF XY: 0.735 AC XY: 100 AN XY: 136

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.743

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.778

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.659 AC: 72813 AN: 110529 Hom.: 17035 Cov.: 23 AF XY: 0.657 AC XY: 21550 AN XY: 32779

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.692

Alfa AF: 0.477 Hom.: 1983

Bravo AF: 0.654

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.5

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs518147; hg19: chrX-113818582;