dbSNP rs770227577: PIK3R4:p.Asp1100Asn (chr3-130686388-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_014602.3(PIK3R4):c.3298G>A(p.Asp1100Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,978 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PIK3R4
NM_014602.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59

Publications

0 publications found

Variant links:

Genes affected

PIK3R4 (HGNC:8982): (phosphoinositide-3-kinase regulatory subunit 4) Predicted to enable protein serine/threonine kinase activity. Involved in positive regulation of phosphatidylinositol 3-kinase activity; receptor catabolic process; and regulation of cytokinesis. Located in late endosome and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

PIK3R4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.849

BS2

High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014602.3. 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
	PIK3R4	NM_014602.3	MANE Select	c.3298G>A	p.Asp1100Asn	missense	Exon 15 of 20	NP_055417.1	Q99570

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3R4	ENST00000356763.8	TSL:1 MANE Select	c.3298G>A	p.Asp1100Asn	missense	Exon 15 of 20	ENSP00000349205.3	Q99570
PIK3R4	ENST00000954554.1		c.3304G>A	p.Asp1102Asn	missense	Exon 15 of 20	ENSP00000624613.1
PIK3R4	ENST00000893860.1		c.3289G>A	p.Asp1097Asn	missense	Exon 15 of 20	ENSP00000563919.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459978

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110308

Other (OTH)

AF:

0.00

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

PhyloP100

7.6

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.28

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.90

MutPred

0.57

Gain of sheet (P = 0.0344)

MVP

0.65

MPC

0.87

ClinPred

0.98

GERP RS

5.1

Varity_R

0.56

gMVP

0.55

Mutation Taster

=55/45

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over