Genetic Variant PTPN3:p.Ala90Thr (chr9-109457194-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002829.4(PTPN3):c.268G>A(p.Ala90Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27415752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN3	NM_002829.4 link	c.268G>A	p.Ala90Thr	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>A	p.Ala90Thr	missense_variant	Exon 4 of 26	5	NM_002829.4	ENSP00000363667.1		P26045-1
PTPN3	ENST00000262539.7 link	c.268G>A	p.Ala90Thr	missense_variant	Exon 4 of 26	5		ENSP00000262539.4		J3KN34

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727134

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111812

Other (OTH)

AF:

0.00

AC:

AN:

60380

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.014

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

-0.42

.;N

PhyloP100

5.9

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.040

.;N

REVEL

Benign

0.22

Sift

Benign

0.036

.;D

Sift4G

Uncertain

0.028

D;T

Polyphen

0.0010

.;B

Vest4

0.21

MutPred

0.32

Gain of phosphorylation at A90 (P = 0.04);Gain of phosphorylation at A90 (P = 0.04);

MVP

0.77

MPC

0.22

ClinPred

0.92

GERP RS

5.6

Varity_R

0.20

gMVP

0.15

Mutation Taster

=95/5

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over