Variant 16-1241307-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003294.4(TPSAB1):c.216A>G(p.Ala72Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 94,578 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 Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 0 hom., cov: 35)

Exomes 𝑓: 0.14 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

TPSAB1
NM_003294.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -11.8

Variant links:

Genes affected

TPSAB1 (HGNC:12019): (tryptase alpha/beta 1) 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, alpha and beta 1. 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]

TPSAB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 16-1241307-A-G is Benign according to our data. Variant chr16-1241307-A-G is described in ClinVar as [Benign]. Clinvar id is 1244990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-11.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPSAB1	NM_003294.4 link	c.216A>G	p.Ala72Ala	synonymous_variant	3/6	ENST00000338844.8	NP_003285.2	Q15661-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPSAB1	ENST00000338844.8 link	c.216A>G	p.Ala72Ala	synonymous_variant	3/6	1	NM_003294.4	ENSP00000343577.3		Q15661-1

Frequencies

GnomAD3 genomes

AF:

0.0644

AC:

6088

AN:

94504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.0519

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.0791

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.0857

Gnomad NFE

AF:

0.0744

Gnomad OTH

AF:

0.0629

GnomAD3 exomes

AF:

0.0444

AC:

6872

AN:

154736

Hom.:

AF XY:

0.0446

AC XY:

3707

AN XY:

83178

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0274

Gnomad ASJ exome

AF:

0.0545

Gnomad EAS exome

AF:

0.0433

Gnomad SAS exome

AF:

0.0546

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0443

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

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

AF:

0.143

AC:

112556

AN:

785852

Hom.:

Cov.:

154

AF XY:

0.137

AC XY:

53676

AN XY:

393028

show subpopulations

Gnomad4 AFR exome

AF:

0.0560

Gnomad4 AMR exome

AF:

0.0445

Gnomad4 ASJ exome

AF:

0.0766

Gnomad4 EAS exome

AF:

0.0836

Gnomad4 SAS exome

AF:

0.0829

Gnomad4 FIN exome

AF:

0.0920

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.0644

AC:

6089

AN:

94578

Hom.:

Cov.:

AF XY:

0.0659

AC XY:

3054

AN XY:

46352

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.0520

Gnomad4 ASJ

AF:

0.0550

Gnomad4 EAS

AF:

0.152

Gnomad4 SAS

AF:

0.0795

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.0744

Gnomad4 OTH

AF:

0.0634

Alfa

AF:

0.0891

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.41

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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