3-179201469-G-C

Position:

• chr3-179201469-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_006218.4(PIK3CA):​c.742G>C​(p.Gly248Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G248S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3CA NM_006218.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.45

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PIK3CA

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.742G>C	p.Gly248Arg	missense_variant	4/21	ENST00000263967.4
PIK3CA	XM_006713658.5	c.742G>C	p.Gly248Arg	missense_variant	4/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.742G>C	p.Gly248Arg	missense_variant	4/21	2	NM_006218.4	P1
PIK3CA	ENST00000643187.1	c.742G>C	p.Gly248Arg	missense_variant	4/22
PIK3CA	ENST00000675467.1	n.3549G>C		non_coding_transcript_exon_variant	3/20
PIK3CA	ENST00000675786.1	c.742G>C	p.Gly248Arg	missense_variant, NMD_transcript_variant	4/21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.3	N;.
REVEL	Uncertain	0.41
Sift	Benign	0.23	T;.
Sift4G	Benign	0.36	T;.
Polyphen		0.98	D;.
Vest4		0.83
MutPred		0.57		Gain of methylation at K253 (P = 0.0528);Gain of methylation at K253 (P = 0.0528);
MVP		0.83
MPC		1.5
ClinPred		0.74	D
GERP RS		5.6
Varity_R		0.61
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-178919257;