Genetic Variant NM_002829.4:c.268G>C (chr9-109457194-C-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_002829.4(PTPN3):c.268G>C(p.Ala90Pro) variant causes a missense change. The variant allele was found at a frequency of 0.353 in 1,613,064 control chromosomes in the GnomAD database, including 103,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11430 hom., cov: 33)

Exomes 𝑓: 0.35 ( 91779 hom. )

Consequence

PTPN3
NM_002829.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.93

Publications

31 publications found

Variant links:

Genes affected

PTPN3 (HGNC:9655): (protein tyrosine phosphatase non-receptor type 3) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. P97, a cell cycle regulator involved in a variety of membrane related functions, has been shown to be a substrate of this PTP. This PTP was also found to interact with, and be regulated by adaptor protein 14-3-3 beta. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

PTPN3 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PTPN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.1424584E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN3	NM_002829.4 link	c.268G>C	p.Ala90Pro	missense_variant	Exon 4 of 26	ENST00000374541.4	NP_002820.3	P26045-1B7Z9V1Q8N4S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN3	ENST00000374541.4 link	c.268G>C	p.Ala90Pro	missense_variant	Exon 4 of 26	5	NM_002829.4	ENSP00000363667.1		P26045-1
PTPN3	ENST00000262539.7 link	c.268G>C	p.Ala90Pro	missense_variant	Exon 4 of 26	5		ENSP00000262539.4		J3KN34

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57423

AN:

151984

Hom.:

11402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.357

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.346

AC:

86913

AN:

251060

AF XY:

0.351

show subpopulations

Gnomad AFR exome

AF:

0.493

Gnomad AMR exome

AF:

0.247

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.351

AC:

512375

AN:

1460962

Hom.:

91779

Cov.:

AF XY:

0.353

AC XY:

256410

AN XY:

726844

show subpopulations

African (AFR)

AF:

0.500

AC:

16710

AN:

33444

American (AMR)

AF:

0.255

AC:

11420

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

8138

AN:

26120

East Asian (EAS)

AF:

0.378

AC:

14986

AN:

39698

South Asian (SAS)

AF:

0.436

AC:

37575

AN:

86176

European-Finnish (FIN)

AF:

0.307

AC:

16423

AN:

53412

Middle Eastern (MID)

AF:

0.328

AC:

1891

AN:

5766

European-Non Finnish (NFE)

AF:

0.345

AC:

383836

AN:

1111292

Other (OTH)

AF:

0.354

AC:

21396

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16293

32585

48878

65170

81463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12458

24916

37374

49832

62290

<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:

0.378

AC:

57499

AN:

152102

Hom.:

11430

Cov.:

AF XY:

0.375

AC XY:

27862

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.489

AC:

20256

AN:

41464

American (AMR)

AF:

0.287

AC:

4384

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

1115

AN:

3470

East Asian (EAS)

AF:

0.357

AC:

1845

AN:

5174

South Asian (SAS)

AF:

0.434

AC:

2093

AN:

4822

European-Finnish (FIN)

AF:

0.300

AC:

3174

AN:

10590

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.344

AC:

23411

AN:

67982

Other (OTH)

AF:

0.358

AC:

757

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1854

3708

5561

7415

9269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.350

Hom.:

7144

Bravo

AF:

0.382

TwinsUK

AF:

0.340

AC:

1262

ALSPAC

AF:

0.347

AC:

1338

ESP6500AA

AF:

0.482

AC:

2124

ESP6500EA

AF:

0.339

AC:

2915

ExAC

AF:

0.357

AC:

43295

Asia WGS

AF:

0.406

AC:

1412

AN:

3478

EpiCase

AF:

0.343

EpiControl

AF:

0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.074

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.00091

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.4

.;N

PhyloP100

5.9

PrimateAI

Uncertain

0.59

PROVEAN

Benign

3.8

.;N

REVEL

Uncertain

0.35

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.065

MPC

0.29

ClinPred

0.019

GERP RS

5.6

Varity_R

0.23

gMVP

0.33

Mutation Taster

=96/4

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