Variant 9-129134882-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_178000.3(PTPA):c.548A>C(p.Lys183Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000363 in 1,613,042 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

PTPA
NM_178000.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.82

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010537565).

BP6

Variant 9-129134882-A-C is Benign according to our data. Variant chr9-129134882-A-C is described in ClinVar as [Benign]. Clinvar id is 787347.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPA	NM_178000.3 link	c.548A>C	p.Lys183Thr	missense_variant	6/10	ENST00000393370.7	NP_821067.1	Q15257-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPA	ENST00000393370.7 link	c.548A>C	p.Lys183Thr	missense_variant	6/10	1	NM_178000.3	ENSP00000377036.2		Q15257-2

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

300

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00674

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000501

AC:

126

AN:

251344

Hom.:

AF XY:

0.000434

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00671

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000194

AC:

284

AN:

1460804

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

121

AN XY:

726758

show subpopulations

Gnomad4 AFR exome

AF:

0.00703

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152238

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

166

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00676

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000399

Hom.:

Bravo

AF:

0.00228

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000552

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

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

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.018

MetaRNN

Benign

0.011

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

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

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

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.5

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

REVEL

Benign

0.13

Sift

Uncertain

0.014

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

Sift4G

Uncertain

0.060

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

Polyphen

0.35

B;.;B;B;B;.;.;P;.;.

Vest4

0.39

MVP

0.043

MPC

0.72

ClinPred

0.062

GERP RS

4.2

Varity_R

0.70

gMVP

0.69

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over