rs796052174

chr7-106868135-G-Achr7-106868135-G-Cchr7-106868135-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001282426.2(PIK3CG):c.574G>A(p.Asp192Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PIK3CG NM_001282426.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CG	NM_001282426.2	c.574G>A	p.Asp192Asn	missense_variant	2/11	ENST00000496166.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CG	ENST00000496166.6	c.574G>A	p.Asp192Asn	missense_variant	2/11	1	NM_001282426.2	P1
PIK3CG	ENST00000359195.3	c.574G>A	p.Asp192Asn	missense_variant	2/11	1		P1
PIK3CG	ENST00000440650.6	c.574G>A	p.Asp192Asn	missense_variant	2/11	1		P1
PIK3CG	ENST00000473541.5	c.-187+2709G>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460868 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Uncertain:1

Uncertain significance, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.9	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.26
Sift	Uncertain	0.013	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.97	D;D;D
Vest4		0.87
MutPred		0.36		Loss of ubiquitination at K194 (P = 0.0368);Loss of ubiquitination at K194 (P = 0.0368);Loss of ubiquitination at K194 (P = 0.0368);
MVP		0.74
MPC		1.0
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.71

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

Other links and lift over

dbSNP: rs796052174; hg19: chr7-106508580; COSMIC: COSV63247729;