chr11-113943043-T-C

Position:

• chr11-113943043-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006028.5(HTR3B):​c.758T>C​(p.Leu253Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HTR3B NM_006028.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR3B	NM_006028.5	c.758T>C	p.Leu253Pro	missense_variant	7/9	ENST00000260191.8	NP_006019.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR3B	ENST00000260191.8	c.758T>C	p.Leu253Pro	missense_variant	7/9	1	NM_006028.5	ENSP00000260191.2
HTR3B	ENST00000537778.5	c.725T>C	p.Leu242Pro	missense_variant	6/8	1		ENSP00000443118.1
HTR3B	ENST00000543092.1	c.481-1530T>C		intron_variant		3		ENSP00000440894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2024

The c.758T>C (p.L253P) alteration is located in exon 7 (coding exon 7) of the HTR3B gene. This alteration results from a T to C substitution at nucleotide position 758, causing the leucine (L) at amino acid position 253 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.60	D;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	3.5	M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.7	D;D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.68		Loss of stability (P = 0.0064);.;
MVP		0.97
MPC		0.64
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.96
gMVP		0.94

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: chr11-113813765;