11-113932306-A-C

Position:

• chr11-113932306-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_006028.5(HTR3B):​c.386A>C​(p.Tyr129Ser) variant causes a missense change. The variant allele was found at a frequency of 0.326 in 1,609,780 control chromosomes in the GnomAD database, including 87,633 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (9954 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77679 hom.)
• 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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025437474).
• BP6: Variant 11-113932306-A-C is Benign according to our data. Variant chr11-113932306-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3B	NM_006028.5	c.386A>C	p.Tyr129Ser	missense_variant	5/9	ENST00000260191.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3B	ENST00000260191.8	c.386A>C	p.Tyr129Ser	missense_variant	5/9	1	NM_006028.5	P2
HTR3B	ENST00000537778.5	c.353A>C	p.Tyr118Ser	missense_variant	4/8	1		A2
HTR3B	ENST00000543092.1	c.173A>C	p.Tyr58Ser	missense_variant	3/5	3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54166 AN: 151850 Hom.: 9929 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.355

GnomAD3 exomes AF: 0.333 AC: 83424 AN: 250544 Hom.: 14563 AF XY: 0.335 AC XY: 45292 AN XY: 135364

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.161

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.334

GnomAD4 exome AF: 0.323 AC: 471301 AN: 1457812 Hom.: 77679 Cov.: 32 AF XY: 0.326 AC XY: 236649 AN XY: 725386

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.357 AC: 54235 AN: 151968 Hom.: 9954 Cov.: 32 AF XY: 0.357 AC XY: 26521 AN XY: 74280

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.354

Alfa AF: 0.327 Hom.: 17482

Bravo AF: 0.360

TwinsUK AF: 0.321 AC: 1190

ALSPAC AF: 0.310 AC: 1194

ESP6500AA AF: 0.428 AC: 1883

ESP6500EA AF: 0.324 AC: 2783

ExAC AF: 0.337 AC: 40852

Asia WGS AF: 0.311 AC: 1084 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.046
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.26
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.089	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-3.2	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	4.3	N;N
REVEL	Benign	0.25
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.051
MPC		0.14
ClinPred		0.0049	T
GERP RS		4.6
Varity_R		0.080
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs1176744; hg19: chr11-113803028; COSMIC: COSV52743661;