dbSNP rs989902: PTPN13:p.Tyr2081Asp (chr4-86785353-T-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.6241T>G(p.Tyr2081Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,603,776 control chromosomes in the GnomAD database, including 152,871 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 0.52 ( 22507 hom., cov: 31)

Exomes 𝑓: 0.42 ( 130364 hom. )

Consequence

PTPN13
NM_080683.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.399

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=1.943122E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN13	NM_080683.3 link	c.6241T>G	p.Tyr2081Asp	missense_variant	Exon 39 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.6241T>G	p.Tyr2081Asp	missense_variant	Exon 39 of 48	1	NM_080683.3	ENSP00000407249.2		Q12923-1

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78640

AN:

151704

Hom.:

22467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.780

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.424

AC:

104181

AN:

245716

Hom.:

23619

AF XY:

0.411

AC XY:

54829

AN XY:

133282

show subpopulations

Gnomad AFR exome

AF:

0.790

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.416

AC:

604261

AN:

1451954

Hom.:

130364

Cov.:

AF XY:

0.411

AC XY:

296848

AN XY:

722366

show subpopulations

Gnomad4 AFR exome

AF:

0.792

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.472

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.433

Gnomad4 NFE exome

AF:

0.412

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.519

AC:

78734

AN:

151822

Hom.:

22507

Cov.:

AF XY:

0.515

AC XY:

38209

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.780

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.416

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.500

Alfa

AF:

0.433

Hom.:

36303

Bravo

AF:

0.536

TwinsUK

AF:

0.412

AC:

1529

ALSPAC

AF:

0.407

AC:

1568

ESP6500AA

AF:

0.784

AC:

2899

ESP6500EA

AF:

0.420

AC:

3432

ExAC

AF:

0.427

AC:

51610

Asia WGS

AF:

0.366

AC:

1275

AN:

3478

EpiCase

AF:

0.416

EpiControl

AF:

0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.2

DANN

Benign

0.58

DEOGEN2

Benign

0.038

.;.;.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.015

T;T;T;T;.

MetaRNN

Benign

0.0000019

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

.;.;.;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

1.3

N;N;N;N;N

REVEL

Benign

0.060

Sift

Benign

0.23

T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.040

MPC

0.049

ClinPred

0.0087

GERP RS

2.8

Varity_R

0.043

gMVP

0.16

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