Variant rs381309 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_001251851.2(PIK3R5):c.-84T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,613,248 control chromosomes in the GnomAD database, including 144,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18296 hom., cov: 33)

Exomes 𝑓: 0.41 ( 126365 hom. )

Consequence

PIK3R5
NM_001251851.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.372

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:

LOC124903922 (HGNC:):

LOC124903922 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-8888712-A-G is Benign according to our data. Variant chr17-8888712-A-G is described in ClinVar as [Benign]. Clinvar id is 129893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8888712-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3R5	NM_001142633.3 link	c.1075T>C	p.Leu359Leu	synonymous_variant	10/19	ENST00000447110.6	NP_001136105.1	Q8WYR1-1L7RT34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R5	ENST00000447110.6 link	c.1075T>C	p.Leu359Leu	synonymous_variant	10/19	5	NM_001142633.3	ENSP00000392812.1		Q8WYR1-1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71342

AN:

152052

Hom.:

18247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.471

GnomAD3 exomes

AF:

0.402

AC:

99320

AN:

246878

Hom.:

21388

AF XY:

0.399

AC XY:

53446

AN XY:

133790

show subpopulations

Gnomad AFR exome

AF:

0.674

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.497

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.411

AC:

600753

AN:

1461078

Hom.:

126365

Cov.:

AF XY:

0.410

AC XY:

298058

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.675

Gnomad4 AMR exome

AF:

0.395

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.423

GnomAD4 genome

AF:

0.470

AC:

71448

AN:

152170

Hom.:

18296

Cov.:

AF XY:

0.459

AC XY:

34178

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.418

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.471

Alfa

AF:

0.434

Hom.:

18505

Bravo

AF:

0.487

Asia WGS

AF:

0.301

AC:

1045

AN:

3478

EpiCase

AF:

0.417

EpiControl

AF:

0.420

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
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

-0.85

CADD

Benign

7.0

DANN

Benign

0.56

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