Genetic Variant NM_080683.3:c.6241T>G (chr4-86785353-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

55 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.424

AC:

104181

AN:

245716

AF XY:

0.411

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 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

African (AFR)

AF:

0.792

AC:

26360

AN:

33280

American (AMR)

AF:

0.422

AC:

18685

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

12270

AN:

26014

East Asian (EAS)

AF:

0.421

AC:

16649

AN:

39532

South Asian (SAS)

AF:

0.269

AC:

22989

AN:

85564

European-Finnish (FIN)

AF:

0.433

AC:

23110

AN:

53312

Middle Eastern (MID)

AF:

0.422

AC:

2423

AN:

5746

European-Non Finnish (NFE)

AF:

0.412

AC:

455303

AN:

1104214

Other (OTH)

AF:

0.441

AC:

26472

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

16060

32121

48181

64242

80302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14056

28112

42168

56224

70280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.519

AC:

78734

AN:

151822

Hom.:

22507

Cov.:

AF XY:

0.515

AC XY:

38209

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.780

AC:

32347

AN:

41458

American (AMR)

AF:

0.470

AC:

7168

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1641

AN:

3470

East Asian (EAS)

AF:

0.416

AC:

2149

AN:

5166

South Asian (SAS)

AF:

0.281

AC:

1352

AN:

4808

European-Finnish (FIN)

AF:

0.439

AC:

4627

AN:

10536

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27887

AN:

67838

Other (OTH)

AF:

0.500

AC:

1051

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1702

3403

5105

6806

8508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.449

Hom.:

57201

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

(source)

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;.

PhyloP100

0.40

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over