Variant 1-46061926-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_003629.4(PIK3R3):c.764+2dupT variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,612,306 control chromosomes in the GnomAD database, including 19 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 19 hom. )

Consequence

PIK3R3
NM_003629.4 splice_donor, intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 8.67

Variant links:

Genes affected

PIK3R3 (HGNC:8981): (phosphoinositide-3-kinase regulatory subunit 3) Phosphatidylinositol 3-kinase (PI3K) phosphorylates phosphatidylinositol and similar compounds, which then serve as second messengers in growth signaling pathways. PI3K is composed of a catalytic and a regulatory subunit. The protein encoded by this gene represents a regulatory subunit of PI3K. The encoded protein contains two SH2 domains through which it binds activated protein tyrosine kinases to regulate their activity. [provided by RefSeq, Jun 2016]

PIK3R3 links:

P3R3URF-PIK3R3 (HGNC:54999): (P3R3URF-PIK3R3 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring genes LOC110117498 and PIK3R3. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

P3R3URF-PIK3R3 links:

PIK3R3 (HGNC:):

PIK3R3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 1-46061926-T-TA is Benign according to our data. Variant chr1-46061926-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1299992.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 386 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R3	NM_003629.4 linkuse as main transcript	c.764+2dupT		splice_donor_variant, intron_variant		ENST00000262741.10	NP_003620.3	Q92569-1Q8N381

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R3	ENST00000262741.10 linkuse as main transcript	c.764+2dupT		splice_donor_variant, intron_variant		1	NM_003629.4	ENSP00000262741.5		Q92569-1
P3R3URF-PIK3R3	ENST00000540385.2 linkuse as main transcript	c.902+2dupT		splice_donor_variant, intron_variant		2		ENSP00000439913.1		F6TDL0

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

385

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00250

AC:

629

AN:

251118

Hom.:

AF XY:

0.00237

AC XY:

322

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00804

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.000970

Gnomad NFE exome

AF:

0.00422

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00390

AC:

5701

AN:

1459972

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

2765

AN XY:

726426

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00911

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000430

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.00465

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.00253

AC:

386

AN:

152334

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.00241

EpiCase

AF:

0.00365

EpiControl

AF:

0.00350

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: -28

DS_DL_spliceai

0.30

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over