rs73334383

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152309.3(PIK3AP1):c.20C>T(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,582,994 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 20 hom. )

Consequence

PIK3AP1
NM_152309.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.436

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002812177).

BP6

Variant 10-96709977-G-A is Benign according to our data. Variant chr10-96709977-G-A is described in ClinVar as Benign. ClinVar VariationId is 474921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (1547/152216) while in subpopulation AFR AF = 0.0339 (1408/41520). AF 95% confidence interval is 0.0324. There are 29 homozygotes in GnomAd4. There are 746 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1547 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PIK3AP1	NM_152309.3 link	c.20C>T	p.Pro7Leu	missense_variant	Exon 2 of 17	ENST00000339364.10	NP_689522.2
PIK3AP1	XM_011539248.2 link	c.20C>T	p.Pro7Leu	missense_variant	Exon 2 of 16		XP_011537550.1
PIK3AP1	XM_047424566.1 link	c.-515C>T		5_prime_UTR_variant	Exon 3 of 18		XP_047280522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3AP1	ENST00000339364.10 link	c.20C>T	p.Pro7Leu	missense_variant	Exon 2 of 17	1	NM_152309.3	ENSP00000339826.5

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1547

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00688

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.00256

AC:

596

AN:

232892

AF XY:

0.00203

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.00207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.00124

GnomAD4 exome

AF:

0.00105

AC:

1498

AN:

1430778

Hom.:

Cov.:

AF XY:

0.000922

AC XY:

651

AN XY:

706180

show subpopulations

African (AFR)

AF:

0.0330

AC:

1090

AN:

32992

American (AMR)

AF:

0.00276

AC:

120

AN:

43406

Ashkenazi Jewish (ASJ)

AF:

0.0000406

AC:

AN:

24642

East Asian (EAS)

AF:

0.00

AC:

AN:

39108

South Asian (SAS)

AF:

0.000120

AC:

AN:

83476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51740

Middle Eastern (MID)

AF:

0.00126

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.000127

AC:

139

AN:

1090926

Other (OTH)

AF:

0.00222

AC:

131

AN:

58930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

157

235

314

392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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

AF:

0.0102

AC:

1547

AN:

152216

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0339

AC:

1408

AN:

41520

American (AMR)

AF:

0.00680

AC:

104

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68010

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00362

Hom.:

Bravo

AF:

0.0117

ESP6500AA

AF:

0.0298

AC:

128

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.00286

AC:

344

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Infantile spasms

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.088

(source)

DANN

Benign

0.43

DEOGEN2

Benign

0.12

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

PhyloP100

-0.44

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.82

REVEL

Benign

0.011

Sift

Benign

0.51

Sift4G

Benign

0.27

Polyphen

0.0

Vest4

0.031

MVP

0.13

MPC

0.55

ClinPred

0.0017

GERP RS

-9.5

Varity_R

0.057

gMVP

0.31

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over