10-96595617-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_152309.3(PIK3AP1):c.2378C>T(p.Thr793Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,004 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 (★).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.2378C>T | p.Thr793Ile | missense_variant | 17/17 | ENST00000339364.10 | NP_689522.2 | |
LOC105378443 | XR_946220.4 | n.1446+4033G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.2378C>T | p.Thr793Ile | missense_variant | 17/17 | 1 | NM_152309.3 | ENSP00000339826 | P1 | |
PIK3AP1 | ENST00000371109.3 | c.1175C>T | p.Thr392Ile | missense_variant | 10/10 | 1 | ENSP00000360150 | |||
PIK3AP1 | ENST00000371110.6 | c.1844C>T | p.Thr615Ile | missense_variant | 16/16 | 2 | ENSP00000360151 | |||
PIK3AP1 | ENST00000467625.5 | n.575C>T | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248222Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133884
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461004Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 726744
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 793 of the PIK3AP1 protein (p.Thr793Ile). This variant is present in population databases (rs140404891, gnomAD 0.002%). 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: 1360489). 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 isoleucine 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