chr9-129147457-C-T

Variant names:

• chr9-129147457-C-T
• rs2480452
• NM_178000.3:c.965C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178000.3(PTPA):​c.965C>T​(p.Ser322Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0773 in 1,613,576 control chromosomes in the GnomAD database, including 5,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S322S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.063 (421 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5079 hom.)
• Consequence: PTPA NM_178000.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 43 publications found

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]

ENSG00000235007 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017366707).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPA	NM_178000.3	c.965C>T	p.Ser322Leu	missense_variant	Exon 10 of 10	ENST00000393370.7	NP_821067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPA	ENST00000393370.7	c.965C>T	p.Ser322Leu	missense_variant	Exon 10 of 10	1	NM_178000.3	ENSP00000377036.2
ENSG00000235007	ENST00000674648.1	c.108+4905C>T		intron_variant	Intron 2 of 2			ENSP00000502744.1

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9604 AN: 152120 Hom.: 423 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0761

Gnomad OTH AF: 0.0606

GnomAD2 exomes AF: 0.0809 AC: 20125 AN: 248896 AF XY: 0.0828

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.0461

Gnomad ASJ exome AF: 0.0686

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.0777

Gnomad NFE exome AF: 0.0754

Gnomad OTH exome AF: 0.0756

GnomAD4 exome AF: 0.0788 AC: 115097 AN: 1461336 Hom.: 5079 Cov.: 31 AF XY: 0.0796 AC XY: 57867 AN XY: 726998

African (AFR) AF: 0.0120 AC: 403 AN: 33470

American (AMR) AF: 0.0449 AC: 2007 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 1736 AN: 26130

East Asian (EAS) AF: 0.189 AC: 7509 AN: 39692

South Asian (SAS) AF: 0.108 AC: 9338 AN: 86238

European-Finnish (FIN) AF: 0.0818 AC: 4350 AN: 53172

Middle Eastern (MID) AF: 0.0513 AC: 292 AN: 5696

European-Non Finnish (NFE) AF: 0.0759 AC: 84360 AN: 1111852

Other (OTH) AF: 0.0845 AC: 5102 AN: 60368

GnomAD4 genome AF: 0.0630 AC: 9598 AN: 152240 Hom.: 421 Cov.: 32 AF XY: 0.0649 AC XY: 4829 AN XY: 74432

African (AFR) AF: 0.0165 AC: 685 AN: 41572

American (AMR) AF: 0.0536 AC: 820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1058 AN: 5160

South Asian (SAS) AF: 0.121 AC: 585 AN: 4830

European-Finnish (FIN) AF: 0.0813 AC: 862 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0761 AC: 5176 AN: 67996

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0714 Hom.: 1653

Bravo AF: 0.0577

TwinsUK AF: 0.0707 AC: 262

ALSPAC AF: 0.0742 AC: 286

ESP6500AA AF: 0.0197 AC: 87

ESP6500EA AF: 0.0741 AC: 637

ExAC AF: 0.0805 AC: 9769

Asia WGS AF: 0.145 AC: 506 AN: 3478

EpiCase AF: 0.0717

EpiControl AF: 0.0721

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;.;T;.;T;T;.;.;T;T;T;T;T;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	.;D;D;D;D;D;D;D;.;.;.;.;.;D
MetaRNN	Benign	0.0017	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;.;M;.;.;.;.;.;.;.;.;.;.;.
PhyloP100		4.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.2	N;N;N;N;N;D;N;.;D;D;D;D;D;D
REVEL	Benign	0.10
Sift	Uncertain	0.016	D;D;D;D;D;D;D;.;T;T;T;T;T;T
Sift4G	Uncertain	0.049	D;D;D;D;D;D;D;D;T;T;T;T;T;T
Polyphen		0.94	P;D;D;P;.;P;D;.;.;.;.;.;.;.
Vest4		0.075
MPC		0.67
ClinPred		0.019	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.31
gMVP		0.20
Mutation Taster		=98/2	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: rs2480452; hg19: chr9-131909736; COSMIC: COSV61235088; COSMIC: COSV61235088;