rs201193059
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_006218.4(PIK3CA):c.318C>A(p.Gly106Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,592,540 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 6 hom. )
Consequence
PIK3CA
NM_006218.4 synonymous
NM_006218.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.497
Genes affected
PIK3CA (HGNC:8975): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 3-179199143-C-A is Benign according to our data. Variant chr3-179199143-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 259960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179199143-C-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.497 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000236 (36/152250) while in subpopulation SAS AF= 0.00228 (11/4816). AF 95% confidence interval is 0.00128. There are 0 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 6 SM gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3CA | NM_006218.4 | c.318C>A | p.Gly106Gly | synonymous_variant | 2/21 | ENST00000263967.4 | NP_006209.2 | |
PIK3CA | XM_006713658.5 | c.318C>A | p.Gly106Gly | synonymous_variant | 2/21 | XP_006713721.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3CA | ENST00000263967.4 | c.318C>A | p.Gly106Gly | synonymous_variant | 2/21 | 2 | NM_006218.4 | ENSP00000263967.3 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152132Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000611 AC: 139AN: 227650Hom.: 0 AF XY: 0.000736 AC XY: 91AN XY: 123564
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GnomAD4 exome AF: 0.000354 AC: 510AN: 1440290Hom.: 6 Cov.: 31 AF XY: 0.000480 AC XY: 344AN XY: 716120
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GnomAD4 genome AF: 0.000236 AC: 36AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 13, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | PIK3CA: BP4, BS1 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Cowden syndrome 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Cowden syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at