9-129134852-G-A

Position:

• chr9-129134852-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_178000.3(PTPA):​c.518G>A​(p.Arg173Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000802 in 1,614,012 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00069 (12 hom.)
• Consequence: PTPA NM_178000.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.39

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065564215).
• BP6: Variant 9-129134852-G-A is Benign according to our data. Variant chr9-129134852-G-A is described in ClinVar as [Benign]. Clinvar id is 777422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000685 (1002/1461732) while in subpopulation AMR AF= 0.019 (850/44714). AF 95% confidence interval is 0.0179. There are 12 homozygotes in gnomad4_exome. There are 424 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPA	NM_178000.3	c.518G>A	p.Arg173Gln	missense_variant	6/10	ENST00000393370.7	NP_821067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPA	ENST00000393370.7	c.518G>A	p.Arg173Gln	missense_variant	6/10	1	NM_178000.3	ENSP00000377036	P1

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 287 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00274 AC: 689 AN: 251400 Hom.: 7 AF XY: 0.00202 AC XY: 275 AN XY: 135870

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.000685 AC: 1002 AN: 1461732 Hom.: 12 Cov.: 31 AF XY: 0.000583 AC XY: 424 AN XY: 727158

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00192 AC: 292 AN: 152280 Hom.: 0 Cov.: 31 AF XY: 0.00211 AC XY: 157 AN XY: 74444

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.000276 Hom.: 1

Bravo AF: 0.00323

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00200 AC: 243

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.0030	.;T;.;T;.;T;T;.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.075
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	.;D;D;D;D;D;D;D;D;D
MetaRNN	Benign	0.0066	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;.;.;L;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.10	N;N;N;N;N;N;N;N;N;.
REVEL	Benign	0.072
Sift	Benign	0.68	T;T;T;T;T;T;T;T;T;.
Sift4G	Benign	0.59	T;T;T;T;T;T;T;T;T;T
Polyphen		0.011	B;.;B;B;B;.;.;B;.;.
Vest4		0.22
MVP		0.082
MPC		0.65
ClinPred		0.023	T
GERP RS		5.4
Varity_R		0.43
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs4836639; hg19: chr9-131897131;