5-112840665-C-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2
The NM_000038.6(APC):c.5071C>A(p.Pro1691Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1691L) has been classified as Likely benign.
Frequency
Consequence
NM_000038.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.5071C>A | p.Pro1691Thr | missense_variant | 16/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.5071C>A | p.Pro1691Thr | missense_variant | 16/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461654Hom.: 0 Cov.: 63 AF XY: 0.00000550 AC XY: 4AN XY: 727134
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2023 | This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1691 of the APC protein (p.Pro1691Thr). This variant is not present in population databases (gnomAD no frequency). 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: 419787). 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 | Baylor Genetics | Sep 05, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528) - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2022 | The p.P1691T variant (also known as c.5071C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 5071. The proline at codon 1691 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at