11-113932306-A-T

Variant names:

• chr11-113932306-A-T
• rs1176744
• NM_006028.5:c.386A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006028.5(HTR3B):​c.386A>T​(p.Tyr129Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HTR3B NM_006028.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02
• Publications: 0 publications found

Genes affected

HTR3B (HGNC:5298): (5-hydroxytryptamine receptor 3B) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit B 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 is not functional as a homomeric complex, but a pentaheteromeric complex with subunit A (HTR3A) displays the full functional features of this receptor. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08245352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.386A>T	p.Tyr129Phe	missense_variant	Exon 5 of 9	ENST00000260191.8	NP_006019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.386A>T	p.Tyr129Phe	missense_variant	Exon 5 of 9	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.353A>T	p.Tyr118Phe	missense_variant	Exon 4 of 8	1		ENSP00000443118.1
HTR3B	ENST00000543092.1	c.170A>T	p.Tyr57Phe	missense_variant	Exon 3 of 5	3		ENSP00000440894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459984 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726396

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110632

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.69	N;.
PhyloP100		5.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.020	N;N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.045	D;T
Vest4		0.13
ClinPred		0.43	T
GERP RS		4.6
Varity_R		0.36
gMVP		0.52
Mutation Taster		=79/21	polymorphism

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: rs1176744; hg19: chr11-113803028;