chr10-96595629-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_152309.3(PIK3AP1):c.2366C>T(p.Pro789Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P789P) has been classified as Likely benign.
Frequency
Consequence
NM_152309.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.2366C>T | p.Pro789Leu | missense_variant | 17/17 | ENST00000339364.10 | |
LOC105378443 | XR_946220.4 | n.1446+4045G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.2366C>T | p.Pro789Leu | missense_variant | 17/17 | 1 | NM_152309.3 | P1 | |
PIK3AP1 | ENST00000371109.3 | c.1163C>T | p.Pro388Leu | missense_variant | 10/10 | 1 | |||
PIK3AP1 | ENST00000371110.6 | c.1832C>T | p.Pro611Leu | missense_variant | 16/16 | 2 | |||
PIK3AP1 | ENST00000467625.5 | n.563C>T | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152104Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460830Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726628
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74424
ClinVar
Submissions by phenotype
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 789 of the PIK3AP1 protein (p.Pro789Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 1414381). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at