Variant chr3-136001831-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002718.5(PPP2R3A):c.333T>C(p.Asp111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,613,946 control chromosomes in the GnomAD database, including 76,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 5787 hom., cov: 33)

Exomes 𝑓: 0.30 ( 70864 hom. )

Consequence

PPP2R3A
NM_002718.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

PPP2R3A (HGNC:9307): (protein phosphatase 2 regulatory subunit B''alpha) This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 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. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]

PPP2R3A 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=-0.58).

BP6

Variant 3-136001831-T-C is Benign according to our data. Variant chr3-136001831-T-C is described in ClinVar as [Benign]. Clinvar id is 3055572.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R3A	NM_002718.5 linkuse as main transcript	c.333T>C	p.Asp111=	synonymous_variant	2/14	ENST00000264977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R3A	ENST00000264977.8 linkuse as main transcript	c.333T>C	p.Asp111=	synonymous_variant	2/14	1	NM_002718.5	P3	Q06190-1
PPP2R3A	ENST00000490467.5 linkuse as main transcript	c.-213-25001T>C		intron_variant		2			Q06190-3

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40491

AN:

152114

Hom.:

5790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.265

AC:

66223

AN:

250286

Hom.:

10081

AF XY:

0.276

AC XY:

37293

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.216

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.0230

Gnomad SAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.304

AC:

444793

AN:

1461714

Hom.:

70864

Cov.:

AF XY:

0.306

AC XY:

222850

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.0201

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.266

AC:

40508

AN:

152232

Hom.:

5787

Cov.:

AF XY:

0.264

AC XY:

19658

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.348

Gnomad4 EAS

AF:

0.0256

Gnomad4 SAS

AF:

0.284

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.310

Hom.:

17939

Bravo

AF:

0.256

Asia WGS

AF:

0.167

AC:

585

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PPP2R3A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.6

DANN

Benign

0.60

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