chr3-179234232-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006218.4(PIK3CA):c.3075C>T(p.Thr1025Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,613,582 control chromosomes in the GnomAD database, including 989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 91 hom., cov: 32)

Exomes 𝑓: 0.012 ( 898 hom. )

Consequence

PIK3CA
NM_006218.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.01

Publications

56 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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)
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

PIK3CA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-179234232-C-T is Benign according to our data. Variant chr3-179234232-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CA	NM_006218.4	MANE Select	c.3075C>T	p.Thr1025Thr	synonymous	Exon 21 of 21	NP_006209.2	P42336

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3CA	ENST00000263967.4	TSL:2 MANE Select	c.3075C>T	p.Thr1025Thr	synonymous	Exon 21 of 21	ENSP00000263967.3	P42336
PIK3CA	ENST00000955190.1		c.3105C>T	p.Thr1035Thr	synonymous	Exon 21 of 21	ENSP00000625249.1
PIK3CA	ENST00000876545.1		c.3075C>T	p.Thr1025Thr	synonymous	Exon 22 of 22	ENSP00000546604.1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2393

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00401

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.0205

AC:

5104

AN:

248616

AF XY:

0.0255

show subpopulations

Gnomad AFR exome

AF:

0.0313

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00397

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.0124

AC:

18094

AN:

1461380

Hom.:

898

Cov.:

AF XY:

0.0156

AC XY:

11369

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.0380

AC:

1271

AN:

33442

American (AMR)

AF:

0.00231

AC:

103

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26122

East Asian (EAS)

AF:

0.00365

AC:

145

AN:

39672

South Asian (SAS)

AF:

0.127

AC:

10927

AN:

86210

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00937

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00433

AC:

4815

AN:

1111716

Other (OTH)

AF:

0.0127

AC:

768

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

833

1666

2498

3331

4164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

292

584

876

1168

1460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0157

AC:

2395

AN:

152202

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1312

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0329

AC:

1368

AN:

41538

American (AMR)

AF:

0.00255

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00309

AC:

AN:

5178

South Asian (SAS)

AF:

0.133

AC:

640

AN:

4816

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00401

AC:

273

AN:

68010

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

114

228

341

455

569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00415

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

not specified (4)

Cowden syndrome (1)

Cowden syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.9

(source)

DANN

Benign

0.66

PhyloP100

-1.0

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over