rs9872542

Variant names:

• chr3-136001831-T-C
• rs9872542
• NM_002718.5:c.333T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002718.5(PPP2R3A):​c.333T>C​(p.Asp111Asp) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.27 (5787 hom., cov: 33)
  • Exomes 𝑓: 0.30 (70864 hom.)
• Consequence: PPP2R3A NM_002718.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.17
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 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 VariationId is 3055572.Status of the report is no_assertion_criteria_provided, 0 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002718.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R3A	NM_002718.5	MANE Select	c.333T>C	p.Asp111Asp	synonymous	Exon 2 of 14	NP_002709.2
	PPP2R3A	NM_001190447.2		c.-213-25001T>C		intron	N/A	NP_001177376.1	Q06190-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R3A	ENST00000264977.8	TSL:1 MANE Select	c.333T>C	p.Asp111Asp	synonymous	Exon 2 of 14	ENSP00000264977.3	Q06190-1
	PPP2R3A	ENST00000872859.1		c.333T>C	p.Asp111Asp	synonymous	Exon 2 of 14	ENSP00000542918.1
	PPP2R3A	ENST00000872860.1		c.333T>C	p.Asp111Asp	synonymous	Exon 2 of 14	ENSP00000542919.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40491 AN: 152114 Hom.: 5790 Cov.: 33

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

GnomAD2 exomes AF: 0.265 AC: 66223 AN: 250286 AF XY: 0.276

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 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.: 44 AF XY: 0.306 AC XY: 222850 AN XY: 727140

African (AFR) AF: 0.213 AC: 7130 AN: 33474

American (AMR) AF: 0.146 AC: 6525 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9005 AN: 26134

East Asian (EAS) AF: 0.0201 AC: 799 AN: 39698

South Asian (SAS) AF: 0.317 AC: 27298 AN: 86242

European-Finnish (FIN) AF: 0.300 AC: 16005 AN: 53398

Middle Eastern (MID) AF: 0.310 AC: 1787 AN: 5768

European-Non Finnish (NFE) AF: 0.322 AC: 358516 AN: 1111908

Other (OTH) AF: 0.294 AC: 17728 AN: 60390

GnomAD4 genome AF: 0.266 AC: 40508 AN: 152232 Hom.: 5787 Cov.: 33 AF XY: 0.264 AC XY: 19658 AN XY: 74430

African (AFR) AF: 0.218 AC: 9040 AN: 41524

American (AMR) AF: 0.198 AC: 3033 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3468

East Asian (EAS) AF: 0.0256 AC: 133 AN: 5190

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4824

European-Finnish (FIN) AF: 0.294 AC: 3119 AN: 10602

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21732 AN: 68010

Other (OTH) AF: 0.250 AC: 529 AN: 2114

Alfa AF: 0.301 Hom.: 33758

Bravo AF: 0.256

Asia WGS AF: 0.167 AC: 585 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PPP2R3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.6
DANN	Benign	0.60
PhyloP100		1.2
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9872542; hg19: chr3-135720673; COSMIC: COSV53866442;