Variant 3-179148542-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_ModerateBP6_ModerateBS1

The NM_006218.4(PIK3CA):c.-138C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0036 in 152,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0017 ( 0 hom. )

Consequence

PIK3CA
NM_006218.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.808

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 3-179148542-C-T is Benign according to our data. Variant chr3-179148542-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 802024.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00361 (548/151746) while in subpopulation NFE AF= 0.00596 (404/67832). AF 95% confidence interval is 0.00548. There are 1 homozygotes in gnomad4. There are 255 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4 link	c.-138C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 21	ENST00000263967.4	NP_006209.2	P42336Q4LE51
PIK3CA	NM_006218.4 link	c.-138C>T	5_prime_UTR_variant	Exon 1 of 21	ENST00000263967.4	NP_006209.2	P42336Q4LE51
PIK3CA	XM_006713658.5 link	c.-77+323C>T	intron_variant	Intron 1 of 20		XP_006713721.1	P42336Q4LE51

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIK3CA	ENST00000263967 link	c.-138C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 21	2	NM_006218.4	ENSP00000263967.3	P42336
PIK3CA	ENST00000263967 link	c.-138C>T	5_prime_UTR_variant	Exon 1 of 21	2	NM_006218.4	ENSP00000263967.3	P42336
PIK3CA	ENST00000477735.1 link	c.-77+323C>T	intron_variant	Intron 1 of 1	4		ENSP00000418145.1	C9J951
PIK3CA	ENST00000643187.1 link	c.-138C>T	upstream_gene_variant				ENSP00000493507.1	A0A2R8Y2F6

Frequencies

GnomAD3 genomes

AF:

0.00361

AC:

548

AN:

151638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000605

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.000920

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00563

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00596

Gnomad OTH

AF:

0.00192

GnomAD4 exome

AF:

0.00166

AC:

AN:

604

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

AN XY:

448

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00236

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00361

AC:

548

AN:

151746

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

255

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.000919

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00563

Gnomad4 NFE

AF:

0.00596

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.00313

Asia WGS

AF:

0.000289

AC:

AN:

3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cowden syndrome 1

Benign:1

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

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