11-113985959-G-T

Position:

• chr11-113985959-G-T

Variant summary

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

The NM_000869.6(HTR3A):​c.545-56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,600,812 control chromosomes in the GnomAD database, including 345,406 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 0.55 (25060 hom., cov: 31)
  • Exomes 𝑓: 0.66 (320346 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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]

HTR3A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3A	NM_000869.6	c.545-56G>T		intron_variant		ENST00000504030.7	NP_000860.3
HTR3A	NM_213621.4	c.545-56G>T		intron_variant			NP_998786.3
HTR3A	NM_001161772.3	c.500-56G>T		intron_variant			NP_001155244.1
HTR3A	NR_046363.2	n.763-559G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7	c.545-56G>T		intron_variant		1	NM_000869.6	ENSP00000424189.2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82788 AN: 151730 Hom.: 25061 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.660 AC: 956446 AN: 1448964 Hom.: 320346 AF XY: 0.662 AC XY: 477457 AN XY: 721720

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.629

Gnomad4 SAS exome AF: 0.645

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.684

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.545 AC: 82793 AN: 151848 Hom.: 25060 Cov.: 31 AF XY: 0.548 AC XY: 40662 AN XY: 74220

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.563

Alfa AF: 0.647 Hom.: 41980

Bravo AF: 0.522

Asia WGS AF: 0.596 AC: 2072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10160548; hg19: chr11-113856681;