rs1018719222
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_152309.3(PIK3AP1):c.1805C>T(p.Thr602Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T602T) has been classified as Benign.
Frequency
Consequence
NM_152309.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3AP1 | NM_152309.3 | c.1805C>T | p.Thr602Met | missense_variant | 12/17 | ENST00000339364.10 | |
PIK3AP1 | XM_011539248.2 | c.1805C>T | p.Thr602Met | missense_variant | 12/16 | ||
PIK3AP1 | XM_005269499.2 | c.1271C>T | p.Thr424Met | missense_variant | 11/16 | ||
PIK3AP1 | XM_047424566.1 | c.1271C>T | p.Thr424Met | missense_variant | 13/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3AP1 | ENST00000339364.10 | c.1805C>T | p.Thr602Met | missense_variant | 12/17 | 1 | NM_152309.3 | P1 | |
PIK3AP1 | ENST00000371109.3 | c.602C>T | p.Thr201Met | missense_variant | 5/10 | 1 | |||
PIK3AP1 | ENST00000371110.6 | c.1271C>T | p.Thr424Met | missense_variant | 11/16 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461772Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727190
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
ClinVar
Submissions by phenotype
Infantile spasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 05, 2018 | This sequence change replaces threonine with methionine at codon 602 of the PIK3AP1 protein (p.Thr602Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PIK3AP1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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