rs587780592
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_000038.6(APC):c.263G>A(p.Arg88Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,890 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000038.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.263G>A | p.Arg88Gln | missense_variant | 4/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.263G>A | p.Arg88Gln | missense_variant | 4/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152052Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251450Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727220
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74260
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 29, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 21, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 88 of the APC protein (p.Arg88Gln). This variant is present in population databases (rs587780592, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 135692). 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) performed at Invitae indicates that this missense variant is not expected to disrupt APC 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 21, 2023 | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Oct 04, 2016 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 17, 2023 | This missense variant replaces arginine with glutamine at codon 88 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 9/282830 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2023 | 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at