rs139196838
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000038.6(APC):c.295C>A(p.Arg99=) variant causes a synonymous change involving the alteration of a non-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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R99R) has been classified as Likely benign.
Frequency
Consequence
NM_000038.6 synonymous
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 |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.295C>A | p.Arg99= | synonymous_variant | 4/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.295C>A | p.Arg99= | synonymous_variant | 4/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251458Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 22, 2024 | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 469782). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change affects codon 99 of the APC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the APC protein. - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | The c.295C>A variant (also known as p.R99R), located in coding exon 3 of the APC gene, results from a C to A substitution at nucleotide position 295. This nucleotide substitution does not change the arginine at codon 99. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 31, 2022 | - - |
Classic or attenuated familial adenomatous polyposis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at