chr3-138655414-G-C

Variant names:

• chr3-138655414-G-C
• rs372335398
• NM_006219.3:c.3188C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006219.3(PIK3CB):​c.3188C>G​(p.Thr1063Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. T1063I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3CB NM_006219.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

Genes affected

PIK3CB (HGNC:8976): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) This gene encodes an isoform of the catalytic subunit of phosphoinositide 3-kinase (PI3K). These kinases are important in signaling pathways involving receptors on the outer membrane of eukaryotic cells and are named for their catalytic subunit. The encoded protein is the catalytic subunit for PI3Kbeta (PI3KB). PI3KB has been shown to be part of the activation pathway in neutrophils which have bound immune complexes at sites of injury or infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28164327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	NM_006219.3	MANE Select	c.3188C>G	p.Thr1063Arg	missense	Exon 24 of 24	NP_006210.1	P42338
	PIK3CB	NM_001437286.1		c.3188C>G	p.Thr1063Arg	missense	Exon 23 of 23	NP_001424215.1
	PIK3CB	NM_001437287.1		c.3188C>G	p.Thr1063Arg	missense	Exon 25 of 25	NP_001424216.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CB	ENST00000674063.1	MANE Select	c.3188C>G	p.Thr1063Arg	missense	Exon 24 of 24	ENSP00000501150.1	P42338
	PIK3CB	ENST00000477593.6	TSL:5	c.3188C>G	p.Thr1063Arg	missense	Exon 23 of 23	ENSP00000418143.1	P42338
	PIK3CB	ENST00000894539.1		c.3188C>G	p.Thr1063Arg	missense	Exon 25 of 25	ENSP00000564598.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.57	P
Vest4		0.57
MutPred		0.48		Loss of methylation at K1066 (P = 0.0764)
MVP		0.49
MPC		0.72
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.58
gMVP		0.58
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs372335398; hg19: chr3-138374256;