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GeneBe

rs34642975

chr10-96651261-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_152309.3(PIK3AP1):c.975A>G(p.Glu325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,614,204 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

PIK3AP1
NM_152309.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.253
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-96651261-T-C is Benign according to our data. Variant chr10-96651261-T-C is described in ClinVar as [Benign]. Clinvar id is 474934.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.253 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 216 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIK3AP1NM_152309.3 linkuse as main transcriptc.975A>G p.Glu325= synonymous_variant 6/17 ENST00000339364.10
PIK3AP1XM_011539248.2 linkuse as main transcriptc.975A>G p.Glu325= synonymous_variant 6/16
PIK3AP1XM_005269499.2 linkuse as main transcriptc.441A>G p.Glu147= synonymous_variant 5/16
PIK3AP1XM_047424566.1 linkuse as main transcriptc.441A>G p.Glu147= synonymous_variant 7/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIK3AP1ENST00000339364.10 linkuse as main transcriptc.975A>G p.Glu325= synonymous_variant 6/171 NM_152309.3 P1Q6ZUJ8-1
PIK3AP1ENST00000371110.6 linkuse as main transcriptc.441A>G p.Glu147= synonymous_variant 5/162 Q6ZUJ8-2
PIK3AP1ENST00000468783.1 linkuse as main transcriptn.621A>G non_coding_transcript_exon_variant 5/85

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00142
AC:
216
AN:
152246
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00494
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000374
AC:
94
AN:
251466
Hom.:
0
AF XY:
0.000258
AC XY:
35
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00486
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000146
AC:
213
AN:
1461840
Hom.:
2
Cov.:
32
AF XY:
0.000136
AC XY:
99
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00526
Gnomad4 AMR exome
AF:
0.000425
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00143
AC:
218
AN:
152364
Hom.:
0
Cov.:
32
AF XY:
0.00130
AC XY:
97
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.00498
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.00121
Hom.:
0
Bravo
AF:
0.00176
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Infantile spasms Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 27, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
7.5
Dann
Benign
0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34642975; hg19: chr10-98411018; API