Variant 1-46055887-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003629.4(PIK3R3):c.849T>A(p.Asn283Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,607,792 control chromosomes in the GnomAD database, including 397,227 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.72 ( 38932 hom., cov: 29)

Exomes 𝑓: 0.70 ( 358295 hom. )

Consequence

PIK3R3
NM_003629.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

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:):

P3R3URF-PIK3R3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.530216E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R3	NM_003629.4 linkuse as main transcript	c.849T>A	p.Asn283Lys	missense_variant	7/10	ENST00000262741.10	NP_003620.3
P3R3URF-PIK3R3	NM_001303427.2 linkuse as main transcript	c.987T>A	p.Asn329Lys	missense_variant	7/10		NP_001290356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R3	ENST00000262741.10 linkuse as main transcript	c.849T>A	p.Asn283Lys	missense_variant	7/10	1	NM_003629.4	ENSP00000262741	P1	Q92569-1

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108444

AN:

151562

Hom.:

38918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.699

Gnomad AMR

AF:

0.685

Gnomad ASJ

AF:

0.713

Gnomad EAS

AF:

0.669

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.744

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.692

GnomAD3 exomes

AF:

0.694

AC:

172601

AN:

248776

Hom.:

60188

AF XY:

0.691

AC XY:

92954

AN XY:

134612

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.712

Gnomad EAS exome

AF:

0.675

Gnomad SAS exome

AF:

0.613

Gnomad FIN exome

AF:

0.739

Gnomad NFE exome

AF:

0.709

Gnomad OTH exome

AF:

0.687

GnomAD4 exome

AF:

0.700

AC:

1019577

AN:

1456112

Hom.:

358295

Cov.:

AF XY:

0.698

AC XY:

506170

AN XY:

724768

show subpopulations

Gnomad4 AFR exome

AF:

0.745

Gnomad4 AMR exome

AF:

0.666

Gnomad4 ASJ exome

AF:

0.706

Gnomad4 EAS exome

AF:

0.685

Gnomad4 SAS exome

AF:

0.617

Gnomad4 FIN exome

AF:

0.733

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.698

GnomAD4 genome

AF:

0.715

AC:

108493

AN:

151680

Hom.:

38932

Cov.:

AF XY:

0.715

AC XY:

52957

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.750

Gnomad4 AMR

AF:

0.685

Gnomad4 ASJ

AF:

0.713

Gnomad4 EAS

AF:

0.668

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.744

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.683

Alfa

AF:

0.708

Hom.:

28728

Bravo

AF:

0.715

TwinsUK

AF:

0.701

AC:

2601

ALSPAC

AF:

0.701

AC:

2701

ESP6500AA

AF:

0.738

AC:

3252

ESP6500EA

AF:

0.708

AC:

6090

ExAC

AF:

0.694

AC:

84234

Asia WGS

AF:

0.658

AC:

2288

AN:

3478

EpiCase

AF:

0.708

EpiControl

AF:

0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.12

T;T;T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.32

.;.;T;T

MetaRNN

Benign

0.0000035

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.7

N;N;N;.

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.0

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.040

MutPred

0.46

.;.;.;Gain of ubiquitination at N329 (P = 0.0016);

MPC

0.13

ClinPred

0.0048

GERP RS

4.0

Varity_R

0.086

gMVP

0.23

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over