rs201805846
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_152309.3(PIK3AP1):āc.691A>Gā(p.Thr231Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.000039 ( 0 hom. )
Consequence
PIK3AP1
NM_152309.3 missense
NM_152309.3 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 6.57
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 Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAdExome4 at 57 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.691A>G | p.Thr231Ala | missense_variant | 4/17 | ENST00000339364.10 | |
PIK3AP1 | XM_011539248.2 | c.691A>G | p.Thr231Ala | missense_variant | 4/16 | ||
PIK3AP1 | XM_005269499.2 | c.157A>G | p.Thr53Ala | missense_variant | 3/16 | ||
PIK3AP1 | XM_047424566.1 | c.157A>G | p.Thr53Ala | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.691A>G | p.Thr231Ala | missense_variant | 4/17 | 1 | NM_152309.3 | P1 | |
PIK3AP1 | ENST00000371110.6 | c.157A>G | p.Thr53Ala | missense_variant | 3/16 | 2 | |||
PIK3AP1 | ENST00000468783.1 | n.337A>G | non_coding_transcript_exon_variant | 3/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251460Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135900
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GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727240
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 12, 2022 | The c.691A>G (p.T231A) alteration is located in exon 4 (coding exon 4) of the PIK3AP1 gene. This alteration results from a A to G substitution at nucleotide position 691, causing the threonine (T) at amino acid position 231 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 231 of the PIK3AP1 protein (p.Thr231Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PIK3AP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 578581). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at