Variant rs2480452 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178000.3(PTPA):c.965C>T(p.Ser322Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0773 in 1,613,576 control chromosomes in the GnomAD database, including 5,500 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 0.063 ( 421 hom., cov: 32)

Exomes 𝑓: 0.079 ( 5079 hom. )

Consequence

PTPA
NM_178000.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

PTPA (HGNC:9308): (protein phosphatase 2 phosphatase activator) Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

PTPA 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=0.0017366707).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPA	NM_178000.3 linkuse as main transcript	c.965C>T	p.Ser322Leu	missense_variant	10/10	ENST00000393370.7	NP_821067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPA	ENST00000393370.7 linkuse as main transcript	c.965C>T	p.Ser322Leu	missense_variant	10/10	1	NM_178000.3	ENSP00000377036	P1	Q15257-2

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9604

AN:

152120

Hom.:

423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.0538

Gnomad ASJ

AF:

0.0674

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.0813

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0761

Gnomad OTH

AF:

0.0606

GnomAD3 exomes

AF:

0.0809

AC:

20125

AN:

248896

Hom.:

1046

AF XY:

0.0828

AC XY:

11159

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.0461

Gnomad ASJ exome

AF:

0.0686

Gnomad EAS exome

AF:

0.205

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.0754

Gnomad OTH exome

AF:

0.0756

GnomAD4 exome

AF:

0.0788

AC:

115097

AN:

1461336

Hom.:

5079

Cov.:

AF XY:

0.0796

AC XY:

57867

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.0120

Gnomad4 AMR exome

AF:

0.0449

Gnomad4 ASJ exome

AF:

0.0664

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0818

Gnomad4 NFE exome

AF:

0.0759

Gnomad4 OTH exome

AF:

0.0845

GnomAD4 genome

AF:

0.0630

AC:

9598

AN:

152240

Hom.:

421

Cov.:

AF XY:

0.0649

AC XY:

4829

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.0536

Gnomad4 ASJ

AF:

0.0674

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.0813

Gnomad4 NFE

AF:

0.0761

Gnomad4 OTH

AF:

0.0614

Alfa

AF:

0.0748

Hom.:

1250

Bravo

AF:

0.0577

TwinsUK

AF:

0.0707

AC:

262

ALSPAC

AF:

0.0742

AC:

286

ESP6500AA

AF:

0.0197

AC:

ESP6500EA

AF:

0.0741

AC:

637

ExAC

AF:

0.0805

AC:

9769

Asia WGS

AF:

0.145

AC:

506

AN:

3478

EpiCase

AF:

0.0717

EpiControl

AF:

0.0721

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

.;.;T;.;T;T;.;.;T;T;T;T;T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

.;D;D;D;D;D;D;D;.;.;.;.;.;D

MetaRNN

Benign

0.0017

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;.;M;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.000040

P;P;P;P;P;P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.2

N;N;N;N;N;D;N;.;D;D;D;D;D;D

REVEL

Benign

0.10

Sift

Uncertain

0.016

D;D;D;D;D;D;D;.;T;T;T;T;T;T

Sift4G

Uncertain

0.049

D;D;D;D;D;D;D;D;T;T;T;T;T;T

Polyphen

0.94

P;D;D;P;.;P;D;.;.;.;.;.;.;.

Vest4

0.075

MPC

0.67

ClinPred

0.019

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.31

gMVP

0.20

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