3-179234232-C-T

Position:

chr3-179234232-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006218.4(PIK3CA):c.3075C>T(p.Thr1025=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 45468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179234232-C-T is described in Lovd as [Benign]. Variant chr3-179234232-C-T is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3CA	NM_006218.4 linkuse as main transcript	c.3075C>T	p.Thr1025=	synonymous_variant	21/21	ENST00000263967.4	NP_006209.2
PIK3CA	XM_006713658.5 linkuse as main transcript	c.3075C>T	p.Thr1025=	synonymous_variant	21/21		XP_006713721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4 linkuse as main transcript	c.3075C>T	p.Thr1025=	synonymous_variant	21/21	2	NM_006218.4	ENSP00000263967	P1

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

GnomAD3 exomes

AF:

0.0205

AC:

5104

AN:

248616

Hom.:

302

AF XY:

0.0255

AC XY:

3440

AN XY:

134844

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 SAS exome

AF:

0.131

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

Gnomad4 AFR exome

AF:

0.0380

Gnomad4 AMR exome

AF:

0.00231

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00365

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00433

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0157

AC:

2395

AN:

152202

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1312

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0329

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00782

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

EpiCase

AF:

0.00480

EpiControl

AF:

0.00415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 31, 2012	This variant was identified in a blood sample as well as a tumor sample from an individual. As it is therefore not a somatic change it is less likely to play a role in tumorigenesis. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:4

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	This variant is associated with the following publications: (PMID: 23982433) -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Cowden syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Cowden syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.9

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over