rs10988217

Positions:

• chr9-129125837-A-G

Variant summary

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

The NM_178000.3(PTPA):​c.216+2699A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,136 control chromosomes in the GnomAD database, including 18,858 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 0.45 (18858 hom., cov: 32)
• Consequence: PTPA NM_178000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPA	NM_178000.3	c.216+2699A>G		intron_variant		ENST00000393370.7	NP_821067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPA	ENST00000393370.7	c.216+2699A>G		intron_variant		1	NM_178000.3	ENSP00000377036	P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68726 AN: 152018 Hom.: 18856 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68727 AN: 152136 Hom.: 18858 Cov.: 32 AF XY: 0.455 AC XY: 33804 AN XY: 74364

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.498

Alfa AF: 0.557 Hom.: 19504

Bravo AF: 0.427

Asia WGS AF: 0.320 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.79

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: rs10988217; hg19: chr9-131888116;