17-8888686-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001142633.3(PIK3R5):c.1101G>A(p.Ser367Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,550 control chromosomes in the GnomAD database, including 68,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6337 hom., cov: 33)

Exomes 𝑓: 0.28 ( 62374 hom. )

Consequence

PIK3R5
NM_001142633.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.23

Publications

15 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-8888686-C-T is Benign according to our data. Variant chr17-8888686-C-T is described in ClinVar as Benign. ClinVar VariationId is 130136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3R5	NM_001142633.3 link	c.1101G>A	p.Ser367Ser	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.1101G>A	p.Ser367Ser	synonymous_variant	Exon 10 of 19	5	NM_001142633.3	ENSP00000392812.1		Q8WYR1-1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42366

AN:

152122

Hom.:

6320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.298

GnomAD2 exomes

AF:

0.247

AC:

61093

AN:

247466

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.323

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.285

AC:

416200

AN:

1461310

Hom.:

62374

Cov.:

AF XY:

0.280

AC XY:

203550

AN XY:

726920

show subpopulations

African (AFR)

AF:

0.291

AC:

9754

AN:

33478

American (AMR)

AF:

0.251

AC:

11209

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

8348

AN:

26130

East Asian (EAS)

AF:

0.000730

AC:

AN:

39700

South Asian (SAS)

AF:

0.165

AC:

14266

AN:

86254

European-Finnish (FIN)

AF:

0.207

AC:

10980

AN:

53090

Middle Eastern (MID)

AF:

0.250

AC:

1444

AN:

5768

European-Non Finnish (NFE)

AF:

0.309

AC:

343554

AN:

1111804

Other (OTH)

AF:

0.275

AC:

16616

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

17009

34019

51028

68038

85047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11124

22248

33372

44496

55620

<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:

0.279

AC:

42418

AN:

152240

Hom.:

6337

Cov.:

AF XY:

0.268

AC XY:

19966

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.292

AC:

12145

AN:

41530

American (AMR)

AF:

0.301

AC:

4611

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1153

AN:

3472

East Asian (EAS)

AF:

0.00212

AC:

AN:

5192

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4822

European-Finnish (FIN)

AF:

0.189

AC:

2009

AN:

10610

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.303

AC:

20621

AN:

68000

Other (OTH)

AF:

0.296

AC:

624

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1604

3208

4812

6416

8020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.294

Hom.:

9548

Bravo

AF:

0.288

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.310

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

-0.66

CADD

Benign

2.6

(source)

DANN

Benign

0.86

PhyloP100

-3.2

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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