rs6808122

Positions:

• chr3-184055033-G-A
• chr3-184055033-G-C
• chr3-184055033-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130770.3(HTR3C):​c.234+146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 785,828 control chromosomes in the GnomAD database, including 172,596 homozygotes. 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 0.72 (39782 hom., cov: 34)
  • Exomes 𝑓: 0.64 (132814 hom.)
• Consequence: HTR3C NM_130770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

Genes affected

HTR3C (HGNC:24003): (5-hydroxytryptamine receptor 3C) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit C of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. Genes encoding subunits C, D and E form a cluster on chromosome 3. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3C	NM_130770.3	c.234+146G>A		intron_variant		ENST00000318351.2	NP_570126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3C	ENST00000318351.2	c.234+146G>A		intron_variant		1	NM_130770.3	ENSP00000322617	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108827 AN: 152044 Hom.: 39732 Cov.: 34

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.715

GnomAD4 exome AF: 0.642 AC: 406923 AN: 633666 Hom.: 132814 AF XY: 0.639 AC XY: 208149 AN XY: 325564

Gnomad4 AFR exome AF: 0.866

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.732

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.669

Gnomad4 NFE exome AF: 0.620

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.716 AC: 108930 AN: 152162 Hom.: 39782 Cov.: 34 AF XY: 0.718 AC XY: 53399 AN XY: 74384

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.719

Alfa AF: 0.651 Hom.: 16935

Bravo AF: 0.735

Asia WGS AF: 0.728 AC: 2532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6808122; hg19: chr3-183772821; COSMIC: COSV59174219;