17-8881044-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001142633.3(PIK3R5):c.2383-27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,561,406 control chromosomes in the GnomAD database, including 74,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7687 hom., cov: 32)
  • Exomes 𝑓: 0.30 (66877 hom.)
• Consequence: PIK3R5 NM_001142633.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

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]

LOC124903919 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-8881044-A-G is Benign according to our data. Variant chr17-8881044-A-G is described in ClinVar as [Benign]. Clinvar id is 1327033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R5	NM_001142633.3	c.2383-27T>C		intron_variant		ENST00000447110.6
LOC124903919	XR_007065610.1	n.923+2740A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R5	ENST00000447110.6	c.2383-27T>C		intron_variant		5	NM_001142633.3	P4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46710 AN: 151860 Hom.: 7665 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.266 AC: 66590 AN: 250588 Hom.: 10066 AF XY: 0.261 AC XY: 35387 AN XY: 135438

Gnomad AFR exome AF: 0.356

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.000816

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.300 AC: 422890 AN: 1409428 Hom.: 66877 Cov.: 24 AF XY: 0.295 AC XY: 207950 AN XY: 704186

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.000685

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.308 AC: 46764 AN: 151978 Hom.: 7687 Cov.: 32 AF XY: 0.298 AC XY: 22167 AN XY: 74272

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.310

Alfa AF: 0.316 Hom.: 10599

Bravo AF: 0.317

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ataxia with oculomotor apraxia type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.010
Dann	Benign	0.40

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

Other links and lift over

dbSNP: rs4791765; hg19: chr17-8784361; COSMIC: COSV52650685;