rs1062613

Positions:

• chr11-113975284-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-113975284-T-C is Benign according to our data. Variant chr11-113975284-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3A	NM_000869.6	c.-42T>C		5_prime_UTR_variant	1/9	ENST00000504030.7
HTR3A	NM_213621.4	c.-42T>C		5_prime_UTR_variant	1/8
HTR3A	NR_046363.2	n.177T>C		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7	c.-42T>C		5_prime_UTR_variant	1/9	1	NM_000869.6	P1

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

GnomAD3 exomes AF: 0.791 AC: 194143 AN: 245414 Hom.: 77595 AF XY: 0.795 AC XY: 105615 AN XY: 132788

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 SAS exome AF: 0.870

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

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.856

Gnomad4 ASJ exome AF: 0.751

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.868

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.789

Gnomad4 OTH exome AF: 0.779

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

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.736

Alfa AF: 0.764 Hom.: 53524

Bravo AF: 0.714

Asia WGS AF: 0.861 AC: 2996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1062613; hg19: chr11-113846006;