dbSNP rs2230600: PTPN13:p.Ile1522Met (chr4-86769845-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080683.3(PTPN13):c.4566A>G(p.Ile1522Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,134 control chromosomes in the GnomAD database, including 26,340 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.14 ( 2004 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24336 hom. )

Consequence

PTPN13
NM_080683.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.142

Variant links:

Genes affected

PTPN13 (HGNC:9646): (protein tyrosine phosphatase non-receptor type 13) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP is a large intracellular protein. It has a catalytic PTP domain at its C-terminus and two major structural domains: a region with five PDZ domains and a FERM domain that binds to plasma membrane and cytoskeletal elements. This PTP was found to interact with, and dephosphorylate, Fas receptor and IkappaBalpha through the PDZ domains. This suggests it has a role in Fas mediated programmed cell death. This PTP was also shown to interact with GTPase-activating protein, and thus may function as a regulator of Rho signaling pathways. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Oct 2008]

PTPN13 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040934086).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN13	NM_080683.3 link	c.4566A>G	p.Ile1522Met	missense_variant	Exon 29 of 48	ENST00000411767.7	NP_542414.1	Q12923-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN13	ENST00000411767.7 link	c.4566A>G	p.Ile1522Met	missense_variant	Exon 29 of 48	1	NM_080683.3	ENSP00000407249.2		Q12923-1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22000

AN:

152052

Hom.:

2001

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.183

AC:

45635

AN:

249064

Hom.:

4822

AF XY:

0.178

AC XY:

24021

AN XY:

135126

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.306

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.175

AC:

255831

AN:

1460964

Hom.:

24336

Cov.:

AF XY:

0.173

AC XY:

125816

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.0306

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.174

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.145

AC:

22013

AN:

152170

Hom.:

2004

Cov.:

AF XY:

0.148

AC XY:

11030

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.168

Hom.:

5622

Bravo

AF:

0.142

TwinsUK

AF:

0.170

AC:

629

ALSPAC

AF:

0.174

AC:

672

ESP6500AA

AF:

0.0348

AC:

127

ESP6500EA

AF:

0.163

AC:

1331

ExAC

AF:

0.177

AC:

21410

Asia WGS

AF:

0.179

AC:

623

AN:

3476

EpiCase

AF:

0.168

EpiControl

AF:

0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.069

.;.;.;T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.89

D;D;D;D;.

MetaRNN

Benign

0.0041

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

.;.;.;L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.12

N;N;N;N;N

REVEL

Benign

0.025

Sift

Benign

0.22

T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T

Polyphen

0.076

B;B;B;B;B

Vest4

0.16

MPC

0.061

ClinPred

0.010

GERP RS

3.1

Varity_R

0.036

gMVP

0.12

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over