17-8880832-T-C

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.2496-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,612,472 control chromosomes in the GnomAD database, including 62,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7170 hom., cov: 33)
  • Exomes 𝑓: 0.27 (55449 hom.)
• Consequence: PIK3R5 NM_001142633.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.407

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=-0.88).
• BP6: Variant 17-8880832-T-C is Benign according to our data. Variant chr17-8880832-T-C is described in ClinVar as [Benign]. Clinvar id is 1327032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3R5	NM_001142633.3	c.2496-46A>G		intron_variant		ENST00000447110.6
LOC124903919	XR_007065610.1	n.923+2528T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3R5	ENST00000447110.6	c.2496-46A>G		intron_variant		5	NM_001142633.3	P4

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44552 AN: 152034 Hom.: 7145 Cov.: 33

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.283

GnomAD3 exomes AF: 0.242 AC: 60171 AN: 248726 Hom.: 8357 AF XY: 0.236 AC XY: 31728 AN XY: 134488

Gnomad AFR exome AF: 0.388

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.000766

Gnomad SAS exome AF: 0.141

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.268 AC: 391438 AN: 1460320 Hom.: 55449 Cov.: 34 AF XY: 0.263 AC XY: 191218 AN XY: 726380

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.293 AC: 44614 AN: 152152 Hom.: 7170 Cov.: 33 AF XY: 0.284 AC XY: 21151 AN XY: 74370

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.280

Alfa AF: 0.289 Hom.: 7298

Bravo AF: 0.304

Asia WGS AF: 0.0880 AC: 308 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.2
Dann	Benign	0.81

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: rs4791764; hg19: chr17-8784149;