Genetic Variant PIK3R6:p.Arg368Ser (chr17-8828778-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010855.4(PIK3R6):c.1102C>A(p.Arg368Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R368C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PIK3R6
NM_001010855.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.803

Publications

0 publications found

Variant links:

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]

PIK3R6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3R6	NM_001010855.4	MANE Select	c.1102C>A	p.Arg368Ser	missense	Exon 11 of 20	NP_001010855.1	Q5UE93
PIK3R6	NM_001290211.1		c.694C>A	p.Arg232Ser	missense	Exon 11 of 20	NP_001277140.1	B3KRK9
PIK3R6	NR_110865.1		n.1437C>A		non_coding_transcript_exon	Exon 10 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3R6	ENST00000619866.5	TSL:5 MANE Select	c.1102C>A	p.Arg368Ser	missense	Exon 11 of 20	ENSP00000480157.1	Q5UE93
PIK3R6	ENST00000907451.1		c.1102C>A	p.Arg368Ser	missense	Exon 11 of 20	ENSP00000577510.1
PIK3R6	ENST00000907452.1		c.1087C>A	p.Arg363Ser	missense	Exon 11 of 20	ENSP00000577511.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1437072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32878

American (AMR)

AF:

0.00

AC:

AN:

42192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24574

East Asian (EAS)

AF:

0.00

AC:

AN:

39272

South Asian (SAS)

AF:

0.00

AC:

AN:

83588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

9.11e-7

AC:

AN:

1097546

Other (OTH)

AF:

0.00

AC:

AN:

59084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.068

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.83

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.44

PhyloP100

0.80

PrimateAI

Pathogenic

0.80

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.48

MVP

0.51

GERP RS

3.3

Varity_R

0.14

gMVP

0.67

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over