11-113985959-G-T

Variant names:

• chr11-113985959-G-T
• rs10160548
• NM_000869.6:c.545-56G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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=-0.82).
• 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 rank	MANE	Protein	UniProt
HTR3A	NM_000869.6	c.545-56G>T		intron_variant	Intron 5 of 8	ENST00000504030.7	NP_000860.3
HTR3A	NM_213621.4	c.545-56G>T		intron_variant	Intron 5 of 7		NP_998786.3
HTR3A	NM_001161772.3	c.500-56G>T		intron_variant	Intron 5 of 8		NP_001155244.1
HTR3A	NR_046363.2	n.763-559G>T		intron_variant	Intron 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3A	ENST00000504030.7	c.545-56G>T		intron_variant	Intron 5 of 8	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

African (AFR) AF: 0.246 AC: 8157 AN: 33214

American (AMR) AF: 0.494 AC: 22088 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 15012 AN: 26054

East Asian (EAS) AF: 0.629 AC: 24924 AN: 39612

South Asian (SAS) AF: 0.645 AC: 55381 AN: 85902

European-Finnish (FIN) AF: 0.685 AC: 36558 AN: 53362

Middle Eastern (MID) AF: 0.595 AC: 3369 AN: 5658

European-Non Finnish (NFE) AF: 0.684 AC: 753160 AN: 1100588

Other (OTH) AF: 0.631 AC: 37797 AN: 59882

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

African (AFR) AF: 0.266 AC: 11036 AN: 41414

American (AMR) AF: 0.561 AC: 8553 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2010 AN: 3466

East Asian (EAS) AF: 0.620 AC: 3191 AN: 5148

South Asian (SAS) AF: 0.629 AC: 3013 AN: 4792

European-Finnish (FIN) AF: 0.700 AC: 7375 AN: 10534

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.673 AC: 45709 AN: 67936

Other (OTH) AF: 0.563 AC: 1188 AN: 2110

Alfa AF: 0.633 Hom.: 51591

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
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10160548; hg19: chr11-113856681;