11-113975284-T-C

Variant names:

• chr11-113975284-T-C
• rs1062613
• NM_000869.6:c.-42T>C

Variant summary

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

The NM_000869.6(HTR3A):​c.-42T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,608,240 control chromosomes in the GnomAD database, including 497,445 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 (40471 hom., cov: 33)
  • Exomes 𝑓: 0.79 (456974 hom.)
• Consequence: HTR3A NM_000869.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 118 publications found

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A 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. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000869.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.-42T>C		5_prime_UTR	Exon 1 of 9	NP_000860.3
	HTR3A	NR_046363.2		n.177T>C		non_coding_transcript_exon	Exon 1 of 8
	HTR3A	NM_213621.4		c.-42T>C		5_prime_UTR	Exon 1 of 8	NP_998786.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.-42T>C		5_prime_UTR	Exon 1 of 9	ENSP00000424189.2
	HTR3A	ENST00000375498.6	TSL:1	c.-24T>C		5_prime_UTR	Exon 1 of 9	ENSP00000364648.2
	HTR3A	ENST00000355556.6	TSL:2	c.-24T>C		5_prime_UTR	Exon 1 of 8	ENSP00000347754.2

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109319 AN: 152034 Hom.: 40441 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.734

GnomAD2 exomes AF: 0.791 AC: 194143 AN: 245414 AF XY: 0.795

Gnomad AFR exome AF: 0.527

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.750

Gnomad EAS exome AF: 0.862

Gnomad FIN exome AF: 0.763

Gnomad NFE exome AF: 0.782

Gnomad OTH exome AF: 0.787

GnomAD4 exome AF: 0.790 AC: 1150729 AN: 1456088 Hom.: 456974 Cov.: 33 AF XY: 0.793 AC XY: 574422 AN XY: 724308

African (AFR) AF: 0.522 AC: 17456 AN: 33422

American (AMR) AF: 0.856 AC: 38035 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 19569 AN: 26062

East Asian (EAS) AF: 0.874 AC: 34672 AN: 39654

South Asian (SAS) AF: 0.868 AC: 74506 AN: 85860

European-Finnish (FIN) AF: 0.763 AC: 39323 AN: 51526

Middle Eastern (MID) AF: 0.806 AC: 4631 AN: 5748

European-Non Finnish (NFE) AF: 0.789 AC: 875600 AN: 1109160

Other (OTH) AF: 0.779 AC: 46937 AN: 60230

GnomAD4 genome AF: 0.719 AC: 109399 AN: 152152 Hom.: 40471 Cov.: 33 AF XY: 0.721 AC XY: 53630 AN XY: 74370

African (AFR) AF: 0.536 AC: 22229 AN: 41494

American (AMR) AF: 0.795 AC: 12158 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3470

East Asian (EAS) AF: 0.865 AC: 4467 AN: 5164

South Asian (SAS) AF: 0.868 AC: 4187 AN: 4822

European-Finnish (FIN) AF: 0.759 AC: 8035 AN: 10590

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.783 AC: 53251 AN: 67994

Other (OTH) AF: 0.736 AC: 1558 AN: 2116

Alfa AF: 0.758 Hom.: 139294

Bravo AF: 0.714

Asia WGS AF: 0.861 AC: 2996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.40
PromoterAI		0.018	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1062613; hg19: chr11-113846006;