9-129148365-G-A

Variant names:

• chr9-129148365-G-A
• rs913275
• NM_178000.3:c.*901G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178000.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPA	NM_178000.3	MANE Select	c.*901G>A		3_prime_UTR	Exon 10 of 10	NP_821067.1
	PTPA	NM_178001.3		c.*901G>A		3_prime_UTR	Exon 11 of 11	NP_821068.1
	PTPA	NM_021131.5		c.*901G>A		3_prime_UTR	Exon 11 of 11	NP_066954.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPA	ENST00000393370.7	TSL:1 MANE Select	c.*901G>A		3_prime_UTR	Exon 10 of 10	ENSP00000377036.2
	PTPA	ENST00000358994.9	TSL:1	c.*901G>A		3_prime_UTR	Exon 11 of 11	ENSP00000351885.5
	PTPA	ENST00000452489.6	TSL:1	c.*901G>A		3_prime_UTR	Exon 10 of 10	ENSP00000394338.3

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

African (AFR) AF: 0.222 AC: 4 AN: 18

American (AMR) AF: 0.500 AC: 6 AN: 12

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 12 AN: 12

East Asian (EAS) AF: 0.590 AC: 46 AN: 78

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.704 AC: 38 AN: 54

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.700 AC: 318 AN: 454

Other (OTH) AF: 0.625 AC: 25 AN: 40

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

African (AFR) AF: 0.336 AC: 13917 AN: 41466

American (AMR) AF: 0.599 AC: 9159 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2477 AN: 3472

East Asian (EAS) AF: 0.578 AC: 2983 AN: 5160

South Asian (SAS) AF: 0.683 AC: 3300 AN: 4830

European-Finnish (FIN) AF: 0.784 AC: 8313 AN: 10598

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47711 AN: 67954

Other (OTH) AF: 0.601 AC: 1264 AN: 2104

Alfa AF: 0.653 Hom.: 14432

Bravo AF: 0.563

Asia WGS AF: 0.583 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.094
DANN	Benign	0.53
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	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: rs913275; hg19: chr9-131910644;