5-112839053-TGAA-TGAAGAA
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000038.6(APC):c.3468_3470dup(p.Glu1156dup) variant causes a inframe insertion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. H1153H) has been classified as Likely benign.
Frequency
Consequence
NM_000038.6 inframe_insertion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.3468_3470dup | p.Glu1156dup | inframe_insertion | 16/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.3468_3470dup | p.Glu1156dup | inframe_insertion | 16/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250976Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135644
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461802Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727200
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74306
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 30, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2023 | The c.3468_3470dupAGA variant (also known as p.E1157dup), located in coding exon 15 of the APC gene, results from an in-frame duplication of AGA at nucleotide positions 3468 to 3470. This results in the duplication of a glutamic acid residue at codon 1157. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 13, 2022 | This variant causes a duplication of glutamic acid at codon 1157 of the APC protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250976 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. - |
Familial adenomatous polyposis 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 31, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This variant, c.3468_3470dup, results in the insertion of 1 amino acid(s) of the APC protein (p.Glu1157dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs775186654, gnomAD 0.002%). 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: 420248). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2015 | This in-frame duplication of 3 nucleotides in APC is denoted c.3468_3470dupAGA at the cDNA level and p.Glu1157dup (E1157dup) at the protein level. The normal sequence, with the bases that are duplicated in braces, is AAGA[AGA]GAGA. This duplication of a single Glutamic Acid residue occurs at a position that is not conserved and is located in a Serine-rich region, a Beta-catenin binding domain, and a region responsible for down-regulation through a process mediated by direct ubiquitination (Azzopardi 2008, UniProt). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Since in-frame duplications may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider APC Glu1157dup to be a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at