Variant 16-1229429-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024164.6(TPSB2):c.261G>C(p.Arg87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,183,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 9)

Exomes 𝑓: 0.0018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TPSB2
NM_024164.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Variant links:

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]

TPSB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19787222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPSB2	NM_024164.6 linkuse as main transcript	c.261G>C	p.Arg87Ser	missense_variant	4/6	ENST00000606293.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPSB2	ENST00000606293.5 linkuse as main transcript	c.261G>C	p.Arg87Ser	missense_variant	4/6	1	NM_024164.6	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

125

AN:

68376

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00203

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000837

AC:

AN:

66882

Hom.:

AF XY:

0.000960

AC XY:

AN XY:

34392

show subpopulations

Gnomad AFR exome

AF:

0.000426

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000899

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000838

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00182

AC:

2149

AN:

1183002

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

1037

AN XY:

578828

show subpopulations

Gnomad4 AFR exome

AF:

0.000304

Gnomad4 AMR exome

AF:

0.00155

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00246

Gnomad4 NFE exome

AF:

0.00200

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00183

AC:

125

AN:

68462

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

AN XY:

31490

show subpopulations

Gnomad4 AFR

AF:

0.000428

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.00203

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00303

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

ExAC

AF:

0.000359

AC:

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

Aug 06, 2021

The c.261G>C (p.R87S) alteration is located in exon 4 (coding exon 3) of the TPSB2 gene. This alteration results from a G to C substitution at nucleotide position 261, causing the arginine (R) at amino acid position 87 to be replaced by a serine (S). 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

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.20

T;T

MetaSVM

Uncertain

-0.18

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

Sift4G

Uncertain

0.052

T;D

Vest4

0.53

MutPred

0.67

Loss of methylation at R87 (P = 0.0264);.;

MVP

0.030

ClinPred

0.11

GERP RS

-1.6

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over