NM_001142633.3:c.2299+13G>A

Variant names:

• chr17-8881775-C-T
• rs9902600
• NM_001142633.3:c.2299+13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001142633.3(PIK3R5):​c.2299+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,612,678 control chromosomes in the GnomAD database, including 49,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4737 hom., cov: 32)
  • Exomes 𝑓: 0.24 (45238 hom.)
• Consequence: PIK3R5 NM_001142633.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.39
• Publications: 5 publications found

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

LOC124903919 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-8881775-C-T is Benign according to our data. Variant chr17-8881775-C-T is described in ClinVar as Benign. ClinVar VariationId is 257556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R5	NM_001142633.3	MANE Select	c.2299+13G>A		intron	N/A	NP_001136105.1
	PIK3R5	NM_014308.4		c.2299+13G>A		intron	N/A	NP_055123.2
	PIK3R5	NM_001388396.1		c.2296+13G>A		intron	N/A	NP_001375325.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R5	ENST00000447110.6	TSL:5 MANE Select	c.2299+13G>A		intron	N/A	ENSP00000392812.1
	PIK3R5	ENST00000581552.5	TSL:1	c.2299+13G>A		intron	N/A	ENSP00000462433.1
	PIK3R5	ENST00000623421.3	TSL:1	c.1141+13G>A		intron	N/A	ENSP00000485280.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36354 AN: 151772 Hom.: 4733 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.241

GnomAD2 exomes AF: 0.211 AC: 52885 AN: 250808 AF XY: 0.207

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.289

Gnomad EAS exome AF: 0.000652

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.242 AC: 353644 AN: 1460788 Hom.: 45238 Cov.: 32 AF XY: 0.238 AC XY: 172662 AN XY: 726762

African (AFR) AF: 0.255 AC: 8520 AN: 33462

American (AMR) AF: 0.228 AC: 10164 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 7454 AN: 26126

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39696

South Asian (SAS) AF: 0.127 AC: 10941 AN: 86226

European-Finnish (FIN) AF: 0.178 AC: 9494 AN: 53410

Middle Eastern (MID) AF: 0.192 AC: 1109 AN: 5764

European-Non Finnish (NFE) AF: 0.263 AC: 291832 AN: 1111074

Other (OTH) AF: 0.234 AC: 14113 AN: 60354

GnomAD4 genome AF: 0.239 AC: 36372 AN: 151890 Hom.: 4737 Cov.: 32 AF XY: 0.230 AC XY: 17098 AN XY: 74242

African (AFR) AF: 0.258 AC: 10705 AN: 41422

American (AMR) AF: 0.262 AC: 3996 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1042 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.118 AC: 568 AN: 4816

European-Finnish (FIN) AF: 0.161 AC: 1704 AN: 10570

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17414 AN: 67874

Other (OTH) AF: 0.239 AC: 503 AN: 2102

Alfa AF: 0.249 Hom.: 888

Bravo AF: 0.250

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.47
PhyloP100		1.4
PromoterAI		0.027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9902600; hg19: chr17-8785092;