NM_012217.3:c.235G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_012217.3(TPSD1):ā€‹c.235G>Cā€‹(p.Ala79Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0 ( 0 hom., cov: 37)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TPSD1
NM_012217.3 missense

Scores

12
5
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPSD1NM_012217.3 linkc.235G>C p.Ala79Pro missense_variant Exon 2 of 5 ENST00000211076.5 NP_036349.1 Q9BZJ3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPSD1ENST00000211076.5 linkc.235G>C p.Ala79Pro missense_variant Exon 2 of 5 1 NM_012217.3 ENSP00000211076.3 Q9BZJ3-1
TPSD1ENST00000397534.6 linkc.214G>C p.Ala72Pro missense_variant Exon 3 of 6 5 ENSP00000380668.2 A0A0C4DFZ7

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152224
Hom.:
0
Cov.:
37
FAILED QC
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
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1459578
Hom.:
0
Cov.:
130
AF XY:
0.00
AC XY:
0
AN XY:
726052
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
152224
Hom.:
0
Cov.:
37
AF XY:
0.00
AC XY:
0
AN XY:
74382
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.63
.;D
Eigen
Uncertain
0.38
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Pathogenic
0.35
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.3
.;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-4.7
D;D
REVEL
Pathogenic
0.76
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.66
MutPred
0.91
.;Gain of phosphorylation at T78 (P = 0.3111);
MVP
0.89
MPC
0.060
ClinPred
0.99
D
GERP RS
3.0
Varity_R
0.91
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs373075240; hg19: chr16-1306669; API