rs863224538
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000038.6(APC):c.1627-10T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,218 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 Uncertain significance (★★). There are indicators that this mutation may affect the branch point..
Frequency
Consequence
NM_000038.6 splice_polypyrimidine_tract, intron
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.1627-10T>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.1627-10T>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.07e-7 AC: 1AN: 1414878Hom.: 0 Cov.: 23 AF XY: 0.00000141 AC XY: 1AN XY: 706972
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152218Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2021 | 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 disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with APC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 13 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein. - |
Classic or attenuated familial adenomatous polyposis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Apr 03, 2023 | This variant causes a T to A nucleotide substitution at the -10 position of intron 13 of the APC gene. Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 not been identified 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at