Genetic Variant NM_012217.3:c.282G>C (chr16-1256824-G-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_012217.3(TPSD1):c.282G>C(p.Arg94Ser) variant causes a missense 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 38)

Exomes 𝑓: 0.000025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TPSD1
NM_012217.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0570

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31580758).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPSD1	NM_012217.3 link	c.282G>C	p.Arg94Ser	missense_variant	Exon 3 of 5	ENST00000211076.5	NP_036349.1	Q9BZJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPSD1	ENST00000211076.5 link	c.282G>C	p.Arg94Ser	missense_variant	Exon 3 of 5	1	NM_012217.3	ENSP00000211076.3		Q9BZJ3-1
TPSD1	ENST00000397534.6 link	c.261G>C	p.Arg87Ser	missense_variant	Exon 4 of 6	5		ENSP00000380668.2		A0A0C4DFZ7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151776

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000461

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.000479

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000254

AC:

AN:

1457938

Hom.:

Cov.:

162

AF XY:

0.0000331

AC XY:

AN XY:

725246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000321

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000191

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000460

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000948

Hom.:

ExAC

AF:

0.000519

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Bladder exstrophy-epispadias-cloacal extrophy complex

Uncertain:1

Obstetrics and Gynecology Department, Johns Hopkins School Of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.42

MutationAssessor

Benign

-0.23

.;N

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.049

D;D

Polyphen

0.99

.;D

Vest4

0.51

MutPred

0.71

.;Loss of methylation at R94 (P = 0.0514);

MVP

0.70

MPC

0.053

ClinPred

0.36

GERP RS

1.7

Varity_R

0.61

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over