rs779687992

Variant names:

• chr16-1229435-G-A
• rs779687992
• NM_024164.6:c.255C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_024164.6(TPSB2):​c.255C>T​(p.Ala85Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 9)
  • Exomes 𝑓: 0.000091 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPSB2 NM_024164.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.335
• 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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-1229435-G-A is Benign according to our data. Variant chr16-1229435-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.335 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSB2	NM_024164.6	c.255C>T	p.Ala85Ala	synonymous_variant	Exon 4 of 6	ENST00000606293.5	NP_077078.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSB2	ENST00000606293.5	c.255C>T	p.Ala85Ala	synonymous_variant	Exon 4 of 6	1	NM_024164.6	ENSP00000482743.1

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 1 AN: 69082 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000672

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000105 AC: 7 AN: 66722 AF XY: 0.000175

Gnomad AFR exome AF: 0.000213

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000914 AC: 110 AN: 1204022 Hom.: 0 Cov.: 22 AF XY: 0.000131 AC XY: 77 AN XY: 588138

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000169 AC: 4 AN: 23612

American (AMR) AF: 0.0000486 AC: 1 AN: 20588

Ashkenazi Jewish (ASJ) AF: 0.000164 AC: 3 AN: 18326

East Asian (EAS) AF: 0.00 AC: 0 AN: 32434

South Asian (SAS) AF: 0.000883 AC: 53 AN: 60048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33084

Middle Eastern (MID) AF: 0.000296 AC: 1 AN: 3380

European-Non Finnish (NFE) AF: 0.0000468 AC: 45 AN: 962368

Other (OTH) AF: 0.0000598 AC: 3 AN: 50182

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000145 AC: 1 AN: 69168 Hom.: 0 Cov.: 9 AF XY: 0.0000314 AC XY: 1 AN XY: 31830

African (AFR) AF: 0.00 AC: 0 AN: 11784

American (AMR) AF: 0.00 AC: 0 AN: 7162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1984

East Asian (EAS) AF: 0.00 AC: 0 AN: 1058

South Asian (SAS) AF: 0.000676 AC: 1 AN: 1480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 172

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 39132

Other (OTH) AF: 0.00 AC: 0 AN: 870

Alfa AF: 0.000223 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TPSB2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.48
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs779687992; hg19: chr16-1279436;