rs200001957
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_006218.4(PIK3CA):āc.470A>Gā(p.Asn157Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,612,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_006218.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3CA | NM_006218.4 | c.470A>G | p.Asn157Ser | missense_variant | 3/21 | ENST00000263967.4 | |
PIK3CA | XM_006713658.5 | c.470A>G | p.Asn157Ser | missense_variant | 3/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3CA | ENST00000263967.4 | c.470A>G | p.Asn157Ser | missense_variant | 3/21 | 2 | NM_006218.4 | P1 | |
PIK3CA | ENST00000643187.1 | c.470A>G | p.Asn157Ser | missense_variant | 3/22 | ||||
PIK3CA | ENST00000675467.1 | n.3277A>G | non_coding_transcript_exon_variant | 2/20 | |||||
PIK3CA | ENST00000675786.1 | c.470A>G | p.Asn157Ser | missense_variant, NMD_transcript_variant | 3/21 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135352
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1460602Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 726676
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Cowden syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 157 of the PIK3CA protein (p.Asn157Ser). This variant is present in population databases (rs200001957, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PIK3CA-related conditions. ClinVar contains an entry for this variant (Variation ID: 580643). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PIK3CA 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