3-179234719-G-T

Variant names:

• chr3-179234719-G-T
• rs9838117
• NM_006218.4:c.*355G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

PIK3CA Gene-Disease associations (from GenCC):

• overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• megalencephaly-capillary malformation-polymicrogyria syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• vascular malformation

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Cowden disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Cowden syndrome 5

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006218.4. 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
	PIK3CA	NM_006218.4	MANE Select	c.*355G>T		3_prime_UTR	Exon 21 of 21	NP_006209.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CA	ENST00000263967.4	TSL:2 MANE Select	c.*355G>T		3_prime_UTR	Exon 21 of 21	ENSP00000263967.3
	PIK3CA	ENST00000462255.2	TSL:3	n.2585G>T		non_coding_transcript_exon	Exon 11 of 11
	PIK3CA	ENST00000674534.1		n.4470G>T		non_coding_transcript_exon	Exon 15 of 15

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

African (AFR) AF: 0.490 AC: 2047 AN: 4178

American (AMR) AF: 0.297 AC: 829 AN: 2790

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1842 AN: 5404

East Asian (EAS) AF: 0.123 AC: 1412 AN: 11468

South Asian (SAS) AF: 0.275 AC: 223 AN: 812

European-Finnish (FIN) AF: 0.203 AC: 195 AN: 962

Middle Eastern (MID) AF: 0.425 AC: 221 AN: 520

European-Non Finnish (NFE) AF: 0.247 AC: 13925 AN: 56442

Other (OTH) AF: 0.282 AC: 2053 AN: 7280

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

African (AFR) AF: 0.476 AC: 19716 AN: 41378

American (AMR) AF: 0.298 AC: 4524 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1146 AN: 3458

East Asian (EAS) AF: 0.155 AC: 797 AN: 5156

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4802

European-Finnish (FIN) AF: 0.191 AC: 2000 AN: 10454

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15788 AN: 67778

Other (OTH) AF: 0.331 AC: 696 AN: 2100

Alfa AF: 0.255 Hom.: 6422

Bravo AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		0.57
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: rs9838117; hg19: chr3-178952507; COSMIC: COSV55874992;