X-114726966-A-G

Variant names:

• chrX-114726966-A-G
• NM_000868.4:c.30A>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000868.4(HTR2C):​c.30A>G​(p.Ser10Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000102 in 980,910 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 24)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
• Consequence: HTR2C NM_000868.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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]

LOC105373313 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.30A>G	p.Ser10Ser	synonymous_variant	Exon 3 of 6	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.30A>G	p.Ser10Ser	synonymous_variant	Exon 4 of 7		NP_001243689.2
HTR2C	NM_001256761.3	c.30A>G	p.Ser10Ser	synonymous_variant	Exon 3 of 6		NP_001243690.2
LOC105373313	XR_001755943.2	n.728+3656T>C		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.30A>G	p.Ser10Ser	synonymous_variant	Exon 3 of 6	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.30A>G	p.Ser10Ser	synonymous_variant	Exon 4 of 7	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.30A>G	p.Ser10Ser	synonymous_variant	Exon 3 of 6	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000102 AC: 1 AN: 980910 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 286530

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000130

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-113961375;