16-1229382-G-A

Variant names:

• chr16-1229382-G-A
• rs1370469956
• NM_024164.6:c.308C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_024164.6(TPSB2):​c.308C>T​(p.Pro103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P103R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0000088 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPSB2 NM_024164.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27685517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSB2	NM_024164.6	c.308C>T	p.Pro103Leu	missense_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.308C>T	p.Pro103Leu	missense_variant	Exon 4 of 6	1	NM_024164.6	ENSP00000482743.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 54568 Hom.: 0 Cov.: 7

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000275 AC: 2 AN: 72800 AF XY: 0.0000530

Gnomad AFR exome AF: 0.00

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: 0.0000316

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000876 AC: 7 AN: 799310 Hom.: 0 Cov.: 12 AF XY: 0.00000995 AC XY: 4 AN XY: 401886

African (AFR) AF: 0.0000646 AC: 1 AN: 15486

American (AMR) AF: 0.00 AC: 0 AN: 22594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15986

East Asian (EAS) AF: 0.00 AC: 0 AN: 29840

South Asian (SAS) AF: 0.0000194 AC: 1 AN: 51630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2512

European-Non Finnish (NFE) AF: 0.00000843 AC: 5 AN: 593170

Other (OTH) AF: 0.00 AC: 0 AN: 36286

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 54658 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 24592

African (AFR) AF: 0.00 AC: 0 AN: 8920

American (AMR) AF: 0.00 AC: 0 AN: 5830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1632

East Asian (EAS) AF: 0.00 AC: 0 AN: 806

South Asian (SAS) AF: 0.00 AC: 0 AN: 1142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 164

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31342

Other (OTH) AF: 0.00 AC: 0 AN: 630

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	14
DANN	Benign	0.84
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.20	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.50	T
PhyloP100		-0.35
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.12	T;T
Vest4		0.18
MutPred		0.43		Gain of catalytic residue at Q98 (P = 0.0644);.;
MVP		0.040
ClinPred		0.24	T
GERP RS		1.6
gMVP		0.36
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1370469956; hg19: chr16-1279383;