rs381309

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000623421.3(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
ENST00000623421.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.372

Publications

23 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PIK3R5 links:

ENSG00000297004 (HGNC:):

ENSG00000297004 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 129893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PIK3R5	NM_001142633.3 link	c.1075T>C	p.Leu359Leu	synonymous_variant	Exon 10 of 19	ENST00000447110.6	NP_001136105.1	Q8WYR1-1L7RT34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3R5	ENST00000447110.6 link	c.1075T>C	p.Leu359Leu	synonymous_variant	Exon 10 of 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

GnomAD2 exomes

AF:

0.402

AC:

99320

AN:

246878

AF XY:

0.399

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 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

African (AFR)

AF:

0.675

AC:

22612

AN:

33476

American (AMR)

AF:

0.395

AC:

17636

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

12928

AN:

26130

East Asian (EAS)

AF:

0.193

AC:

7681

AN:

39698

South Asian (SAS)

AF:

0.423

AC:

36445

AN:

86254

European-Finnish (FIN)

AF:

0.304

AC:

16095

AN:

53006

Middle Eastern (MID)

AF:

0.447

AC:

2577

AN:

5768

European-Non Finnish (NFE)

AF:

0.413

AC:

459233

AN:

1111670

Other (OTH)

AF:

0.423

AC:

25546

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

19852

39704

59557

79409

99261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14252

28504

42756

57008

71260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.470

AC:

71448

AN:

152170

Hom.:

18296

Cov.:

AF XY:

0.459

AC XY:

34178

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.665

AC:

27609

AN:

41538

American (AMR)

AF:

0.441

AC:

6735

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1753

AN:

3470

East Asian (EAS)

AF:

0.174

AC:

902

AN:

5178

South Asian (SAS)

AF:

0.418

AC:

2017

AN:

4822

European-Finnish (FIN)

AF:

0.290

AC:

3080

AN:

10608

Middle Eastern (MID)

AF:

0.545

AC:

159

AN:

292

European-Non Finnish (NFE)

AF:

0.408

AC:

27736

AN:

67960

Other (OTH)

AF:

0.471

AC:

993

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1880

3760

5639

7519

9399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.440

Hom.:

23788

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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. -

Ataxia with oculomotor apraxia type 3

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.0

(source)

DANN

Benign

0.56

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over