Variant 16-1229731-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_024164.6(TPSB2):c.68G>T(p.Gly23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 57 hom., cov: 25)

Exomes 𝑓: 0.22 ( 609 hom. )

Failed GnomAD Quality Control

Consequence

TPSB2
NM_024164.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0650

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002231419).

BP6

Variant 16-1229731-C-A is Benign according to our data. Variant chr16-1229731-C-A is described in ClinVar as [Benign]. Clinvar id is 403562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPSB2	NM_024164.6 linkuse as main transcript	c.68G>T	p.Gly23Val	missense_variant	3/6	ENST00000606293.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPSB2	ENST00000606293.5 linkuse as main transcript	c.68G>T	p.Gly23Val	missense_variant	3/6	1	NM_024164.6	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

42146

AN:

128340

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.320

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.286

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.326

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.225

AC:

234565

AN:

1043948

Hom.:

609

Cov.:

AF XY:

0.235

AC XY:

123824

AN XY:

527044

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.413

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.255

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.328

AC:

42166

AN:

128432

Hom.:

Cov.:

AF XY:

0.330

AC XY:

20686

AN XY:

62726

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.320

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.325

Gnomad4 FIN

AF:

0.421

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.228

Hom.:

ExAC

AF:

0.243

AC:

29238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (fails quality filter) -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.50

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

Sift4G

Benign

0.33

T;T

Vest4

0.10

ClinPred

0.019

GERP RS

0.77

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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