rs9838117

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-179234719-G-A
• chr3-179234719-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_006218.4(PIK3CA):​c.*355G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,492 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000198 (3/151492) while in subpopulation AMR AF = 0.000198 (3/15182). AF 95% confidence interval is 0.0000532. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4	c.*355G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5	c.*355G>A		3_prime_UTR_variant	Exon 21 of 21		XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4	c.*355G>A		3_prime_UTR_variant	Exon 21 of 21	2	NM_006218.4	ENSP00000263967.3

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151492 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 89904 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 42046

African (AFR) AF: 0.00 AC: 0 AN: 4180

American (AMR) AF: 0.00 AC: 0 AN: 2790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5412

East Asian (EAS) AF: 0.00 AC: 0 AN: 11472

South Asian (SAS) AF: 0.00 AC: 0 AN: 812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56464

Other (OTH) AF: 0.00 AC: 0 AN: 7288

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151492 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 73948

African (AFR) AF: 0.00 AC: 0 AN: 41272

American (AMR) AF: 0.000198 AC: 3 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67818

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 6422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.4
DANN	Benign	0.49
PhyloP100		0.57

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;