Variant 16-1256897-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012217.3(TPSD1):c.355C>G(p.Gln119Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 40)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TPSD1
NM_012217.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -8.35

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.107248396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPSD1	NM_012217.3 link	c.355C>G	p.Gln119Glu	missense_variant	3/5	ENST00000211076.5	NP_036349.1	Q9BZJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPSD1	ENST00000211076.5 link	c.355C>G	p.Gln119Glu	missense_variant	3/5	1	NM_012217.3	ENSP00000211076.3		Q9BZJ3-1
TPSD1	ENST00000397534.6 link	c.334C>G	p.Gln112Glu	missense_variant	4/6	5		ENSP00000380668.2		A0A0C4DFZ7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461522

Hom.:

Cov.:

167

AF XY:

0.00000413

AC XY:

AN XY:

727064

show subpopulations

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.355C>G (p.Q119E) alteration is located in exon 3 (coding exon 3) of the TPSD1 gene. This alteration results from a C to G substitution at nucleotide position 355, causing the glutamine (Q) at amino acid position 119 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.010

DANN

Benign

0.66

DEOGEN2

Benign

0.058

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.090

.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.24

Sift

Benign

0.10

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.13

.;B

Vest4

0.11

MutPred

0.54

.;Loss of helix (P = 0.3949);

MVP

0.28

MPC

0.0096

ClinPred

0.11

GERP RS

-5.1

Varity_R

0.083

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over