NM_000869.6:c.265-72C>T

Variant names:

• chr11-113981131-C-T
• rs11607240
• NM_000869.6:c.265-72C>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.265-72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 925,392 control chromosomes in the GnomAD database, including 2,833 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 0.058 (380 hom., cov: 32)
  • Exomes 𝑓: 0.073 (2453 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.265-72C>T		intron	N/A	NP_000860.3
	HTR3A	NM_213621.4		c.265-72C>T		intron	N/A	NP_998786.3
	HTR3A	NM_001161772.3		c.220-72C>T		intron	N/A	NP_001155244.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.265-72C>T		intron	N/A	ENSP00000424189.2
	HTR3A	ENST00000375498.6	TSL:1	c.283-72C>T		intron	N/A	ENSP00000364648.2
	HTR3A	ENST00000355556.6	TSL:2	c.283-72C>T		intron	N/A	ENSP00000347754.2

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8780 AN: 152208 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0734 AC: 56739 AN: 773066 Hom.: 2453 Cov.: 10 AF XY: 0.0727 AC XY: 29832 AN XY: 410092

African (AFR) AF: 0.0134 AC: 275 AN: 20460

American (AMR) AF: 0.0695 AC: 2869 AN: 41292

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 667 AN: 21646

East Asian (EAS) AF: 0.000663 AC: 24 AN: 36222

South Asian (SAS) AF: 0.0724 AC: 5098 AN: 70456

European-Finnish (FIN) AF: 0.130 AC: 6792 AN: 52144

Middle Eastern (MID) AF: 0.0375 AC: 112 AN: 2988

European-Non Finnish (NFE) AF: 0.0784 AC: 38411 AN: 490046

Other (OTH) AF: 0.0659 AC: 2491 AN: 37812

GnomAD4 genome AF: 0.0576 AC: 8778 AN: 152326 Hom.: 380 Cov.: 32 AF XY: 0.0593 AC XY: 4418 AN XY: 74488

African (AFR) AF: 0.0145 AC: 601 AN: 41580

American (AMR) AF: 0.0490 AC: 749 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.0640 AC: 309 AN: 4830

European-Finnish (FIN) AF: 0.135 AC: 1437 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5413 AN: 68022

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0622 Hom.: 558

Bravo AF: 0.0487

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.4
DANN	Benign	0.81
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11607240; hg19: chr11-113851853;