dbSNP rs2134181089: PIK3AP1:p.Pro780Leu (chr10-96602301-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152309.3(PIK3AP1):c.2339C>T(p.Pro780Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PIK3AP1
NM_152309.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.98

Publications

0 publications found

Variant links:

Genes affected

PIK3AP1 (HGNC:30034): (phosphoinositide-3-kinase adaptor protein 1) Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in regulation of inflammatory response; regulation of signal transduction; and toll-like receptor signaling pathway. Predicted to be located in cytoplasm and membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PIK3AP1 links:

LOC105378443 (HGNC:):

LOC105378443 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.34996203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3 link	c.2339C>T	p.Pro780Leu	missense_variant	Exon 16 of 17	ENST00000339364.10	NP_689522.2	Q6ZUJ8-1Q86YV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIK3AP1	ENST00000339364.10 link	c.2339C>T	p.Pro780Leu	missense_variant	Exon 16 of 17	1	NM_152309.3	ENSP00000339826.5	Q6ZUJ8-1
PIK3AP1	ENST00000371109.3 link	c.1136C>T	p.Pro379Leu	missense_variant	Exon 9 of 10	1		ENSP00000360150.3	Q6ZUJ8-3
PIK3AP1	ENST00000371110.6 link	c.1805C>T	p.Pro602Leu	missense_variant	Exon 15 of 16	2		ENSP00000360151.2	Q6ZUJ8-2
PIK3AP1	ENST00000467625.5 link	n.536C>T		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452456

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722694

African (AFR)

AF:

0.00

AC:

AN:

32718

American (AMR)

AF:

0.00

AC:

AN:

41646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

84786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108946

Other (OTH)

AF:

0.00

AC:

AN:

59988

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Infantile spasms

Uncertain:1

Sep 01, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

D;.;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.1

M;.;.

PhyloP100

6.0

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0070

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.49

MutPred

0.24

Loss of catalytic residue at P780 (P = 0.0132);.;.;

MVP

0.34

MPC

1.5

ClinPred

0.95

GERP RS

4.2

Varity_R

0.19

gMVP

0.49

Mutation Taster

=63/37

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over