PIK3R6 p.Gly422Arg

Variant names:

• chr17-8828616-C-G
• NM_001010855.4:c.1264G>C
• PIK3R6 p.Gly422Arg

Your query was ambiguous. Multiple possible variants found:

• chr17-8828616-C-G
• chr17-8828616-C-T
• chr17-8828614-TCC-ACG
• chr17-8828614-TCC-GCG
• chr17-8828614-TCC-CCG
• chr17-8828614-TCC-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001010855.4(PIK3R6):​c.1264G>C​(p.Gly422Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIK3R6 NM_001010855.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52
• Publications: 0 publications found

Genes affected

PIK3R6 (HGNC:27101): (phosphoinositide-3-kinase regulatory subunit 6) Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regulatory subunit 5 gene which is located adjacent to this gene on chromosome 7. The orthologous protein in the mouse binds to both the catalytic subunit and to G(beta/gamma), and mediates activation of the kinase subunit downstream of G protein-coupled receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010855.4. 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
	PIK3R6	NM_001010855.4	MANE Select	c.1264G>C	p.Gly422Arg	missense	Exon 11 of 20	NP_001010855.1	Q5UE93
	PIK3R6	NM_001290211.1		c.856G>C	p.Gly286Arg	missense	Exon 11 of 20	NP_001277140.1	B3KRK9
	PIK3R6	NR_110865.1		n.1599G>C		non_coding_transcript_exon	Exon 10 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3R6	ENST00000619866.5	TSL:5 MANE Select	c.1264G>C	p.Gly422Arg	missense	Exon 11 of 20	ENSP00000480157.1	Q5UE93
	PIK3R6	ENST00000907451.1		c.1264G>C	p.Gly422Arg	missense	Exon 11 of 20	ENSP00000577510.1
	PIK3R6	ENST00000907452.1		c.1249G>C	p.Gly417Arg	missense	Exon 11 of 20	ENSP00000577511.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Uncertain	25
DANN	Benign	0.88
DEOGEN2	Pathogenic	0.80	D
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.080	D
MetaRNN	Pathogenic	0.92	D
PhyloP100		3.5
PrimateAI	Pathogenic	0.89	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.19
gMVP		0.91

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-8731933;