16-1229382-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4
The NM_024164.6(TPSB2):c.308C>G(p.Pro103Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/15 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: 7)
Exomes 𝑓: 0.0000025 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TPSB2
NM_024164.6 missense
NM_024164.6 missense
Scores
2
11
Clinical Significance
Conservation
PhyloP100: -0.352
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: Likely_benign. The variant received -1 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.33822644).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TPSB2 | NM_024164.6 | c.308C>G | p.Pro103Arg | missense_variant | Exon 4 of 6 | ENST00000606293.5 | NP_077078.5 |
Ensembl
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 54568Hom.: 0 Cov.: 7
GnomAD3 genomes
AF:
AC:
0
AN:
54568
Hom.:
Cov.:
7
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: 0.00000250 AC: 2AN: 799318Hom.: 0 Cov.: 12 AF XY: 0.00000249 AC XY: 1AN XY: 401888 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
799318
Hom.:
Cov.:
12
AF XY:
AC XY:
1
AN XY:
401888
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
15488
American (AMR)
AF:
AC:
0
AN:
22594
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
15986
East Asian (EAS)
AF:
AC:
0
AN:
29840
South Asian (SAS)
AF:
AC:
1
AN:
51630
European-Finnish (FIN)
AF:
AC:
0
AN:
31806
Middle Eastern (MID)
AF:
AC:
0
AN:
2512
European-Non Finnish (NFE)
AF:
AC:
1
AN:
593174
Other (OTH)
AF:
AC:
0
AN:
36288
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.006664), 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: 54568Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0AN XY: 24502
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
54568
Hom.:
Cov.:
7
AF XY:
AC XY:
0
AN XY:
24502
African (AFR)
AF:
AC:
0
AN:
8850
American (AMR)
AF:
AC:
0
AN:
5810
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
1632
East Asian (EAS)
AF:
AC:
0
AN:
810
South Asian (SAS)
AF:
AC:
0
AN:
1140
European-Finnish (FIN)
AF:
AC:
0
AN:
3854
Middle Eastern (MID)
AF:
AC:
0
AN:
168
European-Non Finnish (NFE)
AF:
AC:
0
AN:
31344
Other (OTH)
AF:
AC:
0
AN:
622
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Jul 30, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.308C>G (p.P103R) 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 308, causing the proline (P) at amino acid position 103 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PhyloP100
PrimateAI
Benign
T
Sift4G
Benign
T;T
Vest4
MutPred
Loss of glycosylation at S105 (P = 0.0764);.;
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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