rs1057519936
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 9P and 1B. PM1PM2PM5PP2PP5_ModerateBP4
The NM_006218.4(PIK3CA):c.3127A>C(p.Met1043Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1043I) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006218.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3CA | NM_006218.4 | c.3127A>C | p.Met1043Leu | missense_variant | 21/21 | ENST00000263967.4 | NP_006209.2 | |
PIK3CA | XM_006713658.5 | c.3127A>C | p.Met1043Leu | missense_variant | 21/21 | XP_006713721.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3CA | ENST00000263967.4 | c.3127A>C | p.Met1043Leu | missense_variant | 21/21 | 2 | NM_006218.4 | ENSP00000263967.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Megalencephaly-capillary malformation-polymicrogyria syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PIK3CA related disorder (ClinVar ID: VCV000376487, PS1_P). A different missense change at the same codon has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000179173,VCV000217292, PMID:28151489,22729224,28151489, PM5_M). he variant is located in a well-established functional domain or exonic hotspot, where pathogenic variants have frequently reported (PM1_M). T In silico tool predictions suggest damaging effect of the variant on gene or gene product (3CNET: 0.954, PP3_P). A missense variant is a common mechanism associated with Megalencephaly-capillary malformation-polymicrogyria syndrome (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.