11-113931385-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_006028.5(HTR3B):c.215A>T(p.Asp72Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000103 in 1,449,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
HTR3B
NM_006028.5 missense, splice_region
NM_006028.5 missense, splice_region
Scores
10
5
4
Splicing: ADA: 0.8109
2
Clinical Significance
Conservation
PhyloP100: 5.70
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.982
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HTR3B | NM_006028.5 | c.215A>T | p.Asp72Val | missense_variant, splice_region_variant | 3/9 | ENST00000260191.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTR3B | ENST00000260191.8 | c.215A>T | p.Asp72Val | missense_variant, splice_region_variant | 3/9 | 1 | NM_006028.5 | P2 | |
HTR3B | ENST00000537778.5 | c.182A>T | p.Asp61Val | missense_variant, splice_region_variant | 2/8 | 1 | A2 | ||
HTR3B | ENST00000543092.1 | c.2A>T | p.Ter1= | coding_sequence_variant | 1/5 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000532 AC: 13AN: 244426Hom.: 0 AF XY: 0.0000303 AC XY: 4AN XY: 132076
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1449658Hom.: 0 Cov.: 28 AF XY: 0.00000693 AC XY: 5AN XY: 721318
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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?
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.215A>T (p.D72V) alteration is located in exon 3 (coding exon 3) of the HTR3B gene. This alteration results from a A to T substitution at nucleotide position 215, causing the aspartic acid (D) at amino acid position 72 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of sheet (P = 0.1158);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at