3-179234719-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006218.4(PIK3CA):c.*355G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 241,382 control chromosomes in the GnomAD database, including 11,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8115 hom., cov: 31)
  • Exomes 𝑓: 0.25 (3121 hom.)
• Consequence: PIK3CA NM_006218.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568

Genes affected

PIK3CA (HGNC:8975): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.*355G>T		3_prime_UTR_variant	21/21	ENST00000263967.4
PIK3CA	XM_006713658.5	c.*355G>T		3_prime_UTR_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.*355G>T		3_prime_UTR_variant	21/21	2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46472 AN: 151408 Hom.: 8101 Cov.: 31

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.253 AC: 22747 AN: 89856 Hom.: 3121 Cov.: 0 AF XY: 0.251 AC XY: 10563 AN XY: 42024

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.307 AC: 46534 AN: 151526 Hom.: 8115 Cov.: 31 AF XY: 0.305 AC XY: 22568 AN XY: 74034

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.331

Alfa AF: 0.251 Hom.: 5222

Bravo AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	1.1
Dann	Benign	0.53

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: rs9838117; hg19: chr3-178952507; COSMIC: COSV55874992; COSMIC: COSV55874992;