16-1229443-G-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024164.6(TPSB2):c.247C>G(p.Leu83Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000812 in 1,231,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 10)
Exomes 𝑓: 8.1e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TPSB2
NM_024164.6 missense
NM_024164.6 missense
Scores
13
Clinical Significance
Conservation
PhyloP100: -0.178
Publications
0 publications found
Genes affected
TPSB2 (HGNC:14120): (tryptase beta 2) Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. These genes are characterized by several distinct features. They have a highly conserved 3' UTR and contain tandem repeat sequences at the 5' flank and 3' UTR which are thought to play a role in regulation of the mRNA stability. These genes have an intron immediately upstream of the initiator Met codon, which separates the site of transcription initiation from protein coding sequence. This feature is characteristic of tryptases but is unusual in other genes. The alleles of this gene exhibit an unusual amount of sequence variation, such that the alleles were once thought to represent two separate genes, beta II and beta III. Beta tryptases appear to be the main isoenzymes expressed in mast cells, whereas in basophils, alpha-tryptases predominate. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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=0.08076185).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TPSB2 | NM_024164.6 | c.247C>G | p.Leu83Val | missense_variant | Exon 4 of 6 | ENST00000606293.5 | NP_077078.5 |
Ensembl
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 78280Hom.: 0 Cov.: 10
GnomAD3 genomes
AF:
AC:
0
AN:
78280
Hom.:
Cov.:
10
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 8.12e-7 AC: 1AN: 1231882Hom.: 0 Cov.: 26 AF XY: 0.00000167 AC XY: 1AN XY: 599574 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1231882
Hom.:
Cov.:
26
AF XY:
AC XY:
1
AN XY:
599574
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
24554
American (AMR)
AF:
AC:
0
AN:
20424
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18478
East Asian (EAS)
AF:
AC:
0
AN:
32628
South Asian (SAS)
AF:
AC:
0
AN:
60954
European-Finnish (FIN)
AF:
AC:
0
AN:
33186
Middle Eastern (MID)
AF:
AC:
0
AN:
3450
European-Non Finnish (NFE)
AF:
AC:
0
AN:
987026
Other (OTH)
AF:
AC:
0
AN:
51182
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00 AC: 0AN: 78280Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0AN XY: 36422
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
78280
Hom.:
Cov.:
10
AF XY:
AC XY:
0
AN XY:
36422
African (AFR)
AF:
AC:
0
AN:
13500
American (AMR)
AF:
AC:
0
AN:
8008
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2202
East Asian (EAS)
AF:
AC:
0
AN:
1292
South Asian (SAS)
AF:
AC:
0
AN:
1646
European-Finnish (FIN)
AF:
AC:
0
AN:
5828
Middle Eastern (MID)
AF:
AC:
0
AN:
180
European-Non Finnish (NFE)
AF:
AC:
0
AN:
44160
Other (OTH)
AF:
AC:
0
AN:
962
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jun 24, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.247C>G (p.L83V) alteration is located in exon 4 (coding exon 3) of the TPSB2 gene. This alteration results from a C to G substitution at nucleotide position 247, causing the leucine (L) at amino acid position 83 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
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PhyloP100
PrimateAI
Benign
T
Sift4G
Benign
T;T
Vest4
MutPred
Gain of methylation at R87 (P = 0.1634);.;
MVP
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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