chr9-129148365-G-A

Position:

• chr9-129148365-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178000.3(PTPA):​c.*901G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,752 control chromosomes in the GnomAD database, including 28,767 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.

• Frequency:
  • Genomes: 𝑓 0.59 (28611 hom., cov: 34)
  • Exomes 𝑓: 0.67 (156 hom.)
• Consequence: PTPA NM_178000.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPA	NM_178000.3	c.*901G>A		3_prime_UTR_variant	10/10	ENST00000393370.7	NP_821067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPA	ENST00000393370.7	c.*901G>A		3_prime_UTR_variant	10/10	1	NM_178000.3	ENSP00000377036	P1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89826 AN: 151960 Hom.: 28613 Cov.: 34

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.671 AC: 452 AN: 674 Hom.: 156 Cov.: 0 AF XY: 0.655 AC XY: 249 AN XY: 380

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.590

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.700

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.591 AC: 89857 AN: 152078 Hom.: 28611 Cov.: 34 AF XY: 0.597 AC XY: 44426 AN XY: 74364

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.601

Alfa AF: 0.656 Hom.: 12045

Bravo AF: 0.563

Asia WGS AF: 0.583 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.094
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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

Other links and lift over

dbSNP: rs913275; hg19: chr9-131910644;