3-136002046-A-C

Variant names:

• chr3-136002046-A-C
• rs752753037
• NM_002718.5:c.548A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002718.5(PPP2R3A):​c.548A>C​(p.Glu183Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E183G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPP2R3A NM_002718.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22501907).

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.548A>C	p.Glu183Ala	missense	Exon 2 of 14	NP_002709.2
	PPP2R3A	NM_001190447.2		c.-213-24786A>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.548A>C	p.Glu183Ala	missense	Exon 2 of 14	ENSP00000264977.3	Q06190-1
	PPP2R3A	ENST00000872859.1		c.548A>C	p.Glu183Ala	missense	Exon 2 of 14	ENSP00000542918.1
	PPP2R3A	ENST00000872860.1		c.548A>C	p.Glu183Ala	missense	Exon 2 of 14	ENSP00000542919.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461598 Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1 AN XY: 727088

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111924

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.070
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.32
MutPred		0.20		Loss of solvent accessibility (P = 0.0062)
MVP		0.082
MPC		0.38
ClinPred		0.80	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.23
Mutation Taster		=79/21	polymorphism

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: rs752753037; hg19: chr3-135720888;