Variant 17-8889197-G-A 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.837C>T(p.His279His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,611,776 control chromosomes in the GnomAD database, including 144,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18266 hom., cov: 33)

Exomes 𝑓: 0.41 ( 126012 hom. )

Consequence

PIK3R5
NM_001142633.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.395

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:

PIK3R5 (HGNC:):

PIK3R5 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=-0.69).

BP6

Variant 17-8889197-G-A is Benign according to our data. Variant chr17-8889197-G-A is described in ClinVar as [Benign]. Clinvar id is 129894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-8889197-G-A 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 linkuse as main transcript	c.837C>T	p.His279His	synonymous_variant	9/19	ENST00000447110.6	NP_001136105.1	Q8WYR1-1L7RT34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3R5	ENST00000447110.6 linkuse as main transcript	c.837C>T	p.His279His	synonymous_variant	9/19	5	NM_001142633.3	ENSP00000392812.1		Q8WYR1-1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71263

AN:

151990

Hom.:

18217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.472

GnomAD3 exomes

AF:

0.401

AC:

100147

AN:

249744

Hom.:

21491

AF XY:

0.398

AC XY:

53772

AN XY:

135070

show subpopulations

Gnomad AFR exome

AF:

0.674

Gnomad AMR exome

AF:

0.386

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.412

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.411

AC:

599225

AN:

1459668

Hom.:

126012

Cov.:

AF XY:

0.409

AC XY:

297278

AN XY:

726190

show subpopulations

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.394

Gnomad4 ASJ exome

AF:

0.494

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.420

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.422

GnomAD4 genome

AF:

0.469

AC:

71369

AN:

152108

Hom.:

18266

Cov.:

AF XY:

0.459

AC XY:

34137

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.440

Gnomad4 ASJ

AF:

0.505

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.408

Gnomad4 OTH

AF:

0.472

Alfa

AF:

0.433

Hom.:

21196

Bravo

AF:

0.486

Asia WGS

AF:

0.298

AC:

1037

AN:

3478

EpiCase

AF:

0.417

EpiControl

AF:

0.419

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

-0.69

CADD

Benign

5.7

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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