TPSB2 p.Val76Leu

Variant names:

• chr16-1229573-C-A
• NM_024164.6:c.226G>T
• TPSB2 p.Val76Leu

Your query was ambiguous. Multiple possible variants found:

• chr16-1229573-C-A
• chr16-1229573-C-G
• chr16-1229571-CAC-TAA
• chr16-1229571-CAC-AAG
• chr16-1229571-CAC-GAG
• chr16-1229571-CAC-TAG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024164.6(TPSB2):​c.226G>T​(p.Val76Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPSB2 NM_024164.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.62
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.081331134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024164.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPSB2	NM_024164.6	MANE Select	c.226G>T	p.Val76Leu	missense	Exon 3 of 6	NP_077078.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPSB2	ENST00000606293.5	TSL:1 MANE Select	c.226G>T	p.Val76Leu	missense	Exon 3 of 6	ENSP00000482743.1	P20231
	TPSB2	ENST00000612142.2	TSL:1	c.247G>T	p.Val83Leu	missense	Exon 2 of 5	ENSP00000478695.1	A0A087WUI4
	TPSB2	ENST00000611196.4	TSL:1	n.226G>T		non_coding_transcript_exon	Exon 3 of 8	ENSP00000484461.1	A0A087X1U0

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1356528 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 668848

African (AFR) AF: 0.00 AC: 0 AN: 29090

American (AMR) AF: 0.00 AC: 0 AN: 32994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21542

East Asian (EAS) AF: 0.00 AC: 0 AN: 36108

South Asian (SAS) AF: 0.00 AC: 0 AN: 71962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056874

Other (OTH) AF: 0.00 AC: 0 AN: 55810

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	1.9
DANN	Benign	0.77
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.91	T
PhyloP100		-4.6
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.39	T
gMVP		0.27

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-1279574;