Genetic Variant PIK3AP1:c.1736-1132G>A (chr10-96621689-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152309.3(PIK3AP1):c.1736-1132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,238 control chromosomes in the GnomAD database, including 12,360 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12342 hom., cov: 32)

Exomes 𝑓: 0.44 ( 18 hom. )

Consequence

PIK3AP1
NM_152309.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

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:

RPS2P36 (HGNC:36784): (ribosomal protein S2 pseudogene 36)

RPS2P36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3AP1	NM_152309.3 link	c.1736-1132G>A		intron_variant	Intron 11 of 16	ENST00000339364.10	NP_689522.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PIK3AP1	ENST00000339364.10 link	c.1736-1132G>A	intron_variant	Intron 11 of 16	1	NM_152309.3	ENSP00000339826.5
PIK3AP1	ENST00000371109.3 link	c.533-1132G>A	intron_variant	Intron 4 of 9	1		ENSP00000360150.3
RPS2P36	ENST00000456516.1 link	n.19G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
PIK3AP1	ENST00000371110.6 link	c.1202-1132G>A	intron_variant	Intron 10 of 15	2		ENSP00000360151.2

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60494

AN:

151946

Hom.:

12340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.428

GnomAD4 exome

AF:

0.436

AC:

AN:

172

Hom.:

Cov.:

AF XY:

0.471

AC XY:

AN XY:

102

show subpopulations

African (AFR)

AF:

0.375

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.466

AC:

AN:

116

Other (OTH)

AF:

0.417

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.398

AC:

60523

AN:

152066

Hom.:

12342

Cov.:

AF XY:

0.399

AC XY:

29665

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.374

AC:

15510

AN:

41480

American (AMR)

AF:

0.453

AC:

6909

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

1844

AN:

3470

East Asian (EAS)

AF:

0.329

AC:

1698

AN:

5168

South Asian (SAS)

AF:

0.485

AC:

2337

AN:

4820

European-Finnish (FIN)

AF:

0.351

AC:

3716

AN:

10576

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.401

AC:

27222

AN:

67968

Other (OTH)

AF:

0.428

AC:

904

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1888

3777

5665

7554

9442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.415

Hom.:

17008

Bravo

AF:

0.405

Asia WGS

AF:

0.452

AC:

1572

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.7

(source)

DANN

Benign

0.79

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over