Variant 9-129142498-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_178000.3(PTPA):c.840C>T(p.Ala280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,612,260 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 26 hom. )

Consequence

PTPA
NM_178000.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.41

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 9-129142498-C-T is Benign according to our data. Variant chr9-129142498-C-T is described in ClinVar as [Benign]. Clinvar id is 731186.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.41 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0029 (4228/1459988) while in subpopulation MID AF= 0.0239 (138/5762). AF 95% confidence interval is 0.0207. There are 26 homozygotes in gnomad4_exome. There are 2228 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPA	NM_178000.3 linkuse as main transcript	c.840C>T	p.Ala280=	synonymous_variant	9/10	ENST00000393370.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPA	ENST00000393370.7 linkuse as main transcript	c.840C>T	p.Ala280=	synonymous_variant	9/10	1	NM_178000.3	P1	Q15257-2

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

571

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00346

AC:

867

AN:

250778

Hom.:

AF XY:

0.00336

AC XY:

456

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.000925

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00622

GnomAD4 exome

AF:

0.00290

AC:

4228

AN:

1459988

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

2228

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.0303

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.000936

Gnomad4 NFE exome

AF:

0.00237

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.00373

AC:

568

AN:

152272

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

269

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00547

Hom.:

Bravo

AF:

0.00400

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00445

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

Invitae

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.6

DANN

Benign

0.64

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