rs200762923
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_006218.4(PIK3CA):c.476C>T(p.Pro159Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,460,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P159P) has been classified as Likely benign.
Frequency
Consequence
NM_006218.4 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 |
---|---|---|---|---|---|---|---|
PIK3CA | NM_006218.4 | c.476C>T | p.Pro159Leu | missense_variant | 3/21 | ENST00000263967.4 | |
PIK3CA | XM_006713658.5 | c.476C>T | p.Pro159Leu | missense_variant | 3/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3CA | ENST00000263967.4 | c.476C>T | p.Pro159Leu | missense_variant | 3/21 | 2 | NM_006218.4 | P1 | |
PIK3CA | ENST00000643187.1 | c.476C>T | p.Pro159Leu | missense_variant | 3/22 | ||||
PIK3CA | ENST00000675467.1 | n.3283C>T | non_coding_transcript_exon_variant | 2/20 | |||||
PIK3CA | ENST00000675786.1 | c.476C>T | p.Pro159Leu | missense_variant, NMD_transcript_variant | 3/21 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460294Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726556
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
PIK3CA-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 01, 2023 | The PIK3CA c.476C>T variant is predicted to result in the amino acid substitution p.Pro159Leu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Cowden syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). ClinVar contains an entry for this variant (Variation ID: 403905). This variant has not been reported in the literature in individuals affected with PIK3CA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 159 of the PIK3CA protein (p.Pro159Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at