11-113932306-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006028.5(HTR3B):​c.386A>G​(p.Tyr129Cys) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y129S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR3B NM_006028.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12177798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.386A>G	p.Tyr129Cys	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>G	p.Tyr129Cys	missense_variant	Exon 5 of 9	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.353A>G	p.Tyr118Cys	missense_variant	Exon 4 of 8	1		ENSP00000443118.1
HTR3B	ENST00000543092.1	c.170A>G	p.Tyr57Cys	missense_variant	Exon 3 of 5	3		ENSP00000440894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.081	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.94	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.0090	B;B
Vest4		0.14
MutPred		0.41		Loss of sheet (P = 0.0357);.;
MVP		0.64
MPC		0.12
ClinPred		0.44	T
GERP RS		4.6
Varity_R		0.18
gMVP		0.55

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-113803028;