Variant 20-50581336-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002827.4(PTPN1):c.1160C>T(p.Pro387Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,614,032 control chromosomes in the GnomAD database, including 26 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0049 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 23 hom. )

Consequence

PTPN1
NM_002827.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

PTPN1 (HGNC:9642): (protein tyrosine phosphatase non-receptor type 1) The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

PTPN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034552217).

BS2

High AC in GnomAd4 at 743 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN1	NM_002827.4 link	c.1160C>T	p.Pro387Leu	missense_variant	Exon 9 of 10	ENST00000371621.5	NP_002818.1	P18031A8K3M3
PTPN1	NM_001278618.2 link	c.941C>T	p.Pro314Leu	missense_variant	Exon 8 of 9		NP_001265547.1	P18031B4DSN5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN1	ENST00000371621.5 link	c.1160C>T	p.Pro387Leu	missense_variant	Exon 9 of 10	1	NM_002827.4	ENSP00000360683.3		P18031
PTPN1	ENST00000541713.5 link	c.941C>T	p.Pro314Leu	missense_variant	Exon 8 of 9	2		ENSP00000437732.1		B4DSN5

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

743

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00734

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00475

AC:

1194

AN:

251178

Hom.:

AF XY:

0.00493

AC XY:

670

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00499

Gnomad NFE exome

AF:

0.00762

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00593

AC:

8668

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

4215

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.00364

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00451

Gnomad4 NFE exome

AF:

0.00697

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152310

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

334

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.00734

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00652

Hom.:

Bravo

AF:

0.00467

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00526

AC:

639

EpiCase

AF:

0.00742

EpiControl

AF:

0.00895

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.6

DANN

Benign

0.70

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.022

Sift

Benign

0.078

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.072

.;B

Vest4

0.047

MVP

0.082

MPC

0.76

ClinPred

0.0044

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.027

gMVP

0.37

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