Genetic Variant TPSD1:p.Ala20Gly (chr16-1256339-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012217.3(TPSD1):c.59C>G(p.Ala20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A20T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 39)

Consequence

TPSD1
NM_012217.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.48

Publications

0 publications found

Variant links:

Genes affected

TPSD1 (HGNC:14118): (tryptase delta 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. Although this gene may be an exception, most of the tryptase 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. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. This gene was once considered to be a pseudogene, although it is now believed to be a functional gene that encodes a protein. [provided by RefSeq, Jul 2008]

TPSD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032977223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012217.3. 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
	TPSD1	NM_012217.3	MANE Select	c.59C>G	p.Ala20Gly	missense	Exon 1 of 5	NP_036349.1	Q9BZJ3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPSD1	ENST00000211076.5	TSL:1 MANE Select	c.59C>G	p.Ala20Gly	missense	Exon 1 of 5	ENSP00000211076.3	Q9BZJ3-1
TPSD1	ENST00000397534.6	TSL:5	c.38C>G	p.Ala13Gly	missense	Exon 2 of 6	ENSP00000380668.2	A0A0C4DFZ7
TPSD1	ENST00000711393.1		c.59C>G	p.Ala20Gly	missense	Exon 1 of 5	ENSP00000518724.1	Q9BZJ3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.010

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.022

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.18

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-0.34

PhyloP100

-3.5

PrimateAI

Uncertain

0.50

PROVEAN

Benign

1.8

REVEL

Benign

0.22

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.088

MutPred

0.25

Gain of phosphorylation at Y24 (P = 0.1943)

MVP

0.27

MPC

0.0096

ClinPred

0.031

GERP RS

-3.6

PromoterAI

-0.050

Neutral

(source)

Varity_R

0.028

gMVP

0.58

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over