Variant rs9903447 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142633.3(PIK3R5):c.2299+18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,248 control chromosomes in the GnomAD database, including 54,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6770 hom., cov: 31)

Exomes 𝑓: 0.25 ( 47255 hom. )

Consequence

PIK3R5
NM_001142633.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.633

Variant links:

Genes affected

PIK3R5 (HGNC:30035): (phosphoinositide-3-kinase regulatory subunit 5) Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. This gene encodes the 101 kD regulatory subunit of the class I PI3K gamma complex, which is a dimeric enzyme, consisting of a 110 kD catalytic subunit gamma and a regulatory subunit of either 55, 87 or 101 kD. This protein recruits the catalytic subunit from the cytosol to the plasma membrane through high-affinity interaction with G-beta-gamma proteins. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found. [provided by RefSeq, Oct 2011]

PIK3R5 links:

LOC124903919 (HGNC:):

LOC124903919 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 17-8881770-A-C is Benign according to our data. Variant chr17-8881770-A-C is described in ClinVar as [Benign]. Clinvar id is 257557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8881770-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R5	NM_001142633.3 linkuse as main transcript	c.2299+18T>G		intron_variant		ENST00000447110.6	NP_001136105.1
LOC124903919	XR_007065610.1 linkuse as main transcript	n.924-2796A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R5	ENST00000447110.6 linkuse as main transcript	c.2299+18T>G		intron_variant		5	NM_001142633.3	ENSP00000392812	P4	Q8WYR1-1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42534

AN:

151490

Hom.:

6764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.401

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.270

GnomAD3 exomes

AF:

0.222

AC:

55607

AN:

250724

Hom.:

7173

AF XY:

0.215

AC XY:

29107

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.163

Gnomad NFE exome

AF:

0.260

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.247

AC:

360117

AN:

1460640

Hom.:

47255

Cov.:

AF XY:

0.241

AC XY:

175485

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.406

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.281

AC:

42568

AN:

151608

Hom.:

6770

Cov.:

AF XY:

0.271

AC XY:

20036

AN XY:

74048

show subpopulations

Gnomad4 AFR

AF:

0.401

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.264

Hom.:

1342

Bravo

AF:

0.297

Asia WGS

AF:

0.0800

AC:

281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Ataxia with oculomotor apraxia type 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.62

DANN

Benign

0.49

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over