NM_001282426.2:c.235C>A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001282426.2(PIK3CG):c.235C>A(p.Leu79Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PIK3CG
NM_001282426.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

PIK3CG (HGNC:8978): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I catalytic subunit of PI3K. Like other class I catalytic subunits (p110-alpha p110-beta, and p110-delta), the encoded protein binds a p85 regulatory subunit to form PI3K. This gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2015]

PIK3CG links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13251597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CG	NM_001282426.2 link	c.235C>A	p.Leu79Met	missense_variant	Exon 2 of 11	ENST00000496166.6	NP_001269355.1	P48736A0A024R720A8K9G9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIK3CG	ENST00000496166.6 link	c.235C>A	p.Leu79Met	missense_variant	Exon 2 of 11	1	NM_001282426.2	ENSP00000419260.1	P48736
PIK3CG	ENST00000359195.3 link	c.235C>A	p.Leu79Met	missense_variant	Exon 2 of 11	1		ENSP00000352121.3	P48736
PIK3CG	ENST00000440650.6 link	c.235C>A	p.Leu79Met	missense_variant	Exon 2 of 11	1		ENSP00000392258.2	P48736
PIK3CG	ENST00000473541.5 link	c.-187+2370C>A		intron_variant	Intron 1 of 6	5		ENSP00000417623.1	E9PDN7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247330

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1460340

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726574

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.235C>A (p.L79M) alteration is located in exon 2 (coding exon 1) of the PIK3CG gene. This alteration results from a C to A substitution at nucleotide position 235, causing the leucine (L) at amino acid position 79 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.17

T;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.48

.;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.37

N;N;N

REVEL

Benign

0.061

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.18

MutPred

0.37

Gain of catalytic residue at L79 (P = 8e-04);Gain of catalytic residue at L79 (P = 8e-04);Gain of catalytic residue at L79 (P = 8e-04);

MVP

0.32

MPC

0.39

ClinPred

0.031

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.064

gMVP

0.24

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