5-112840228-C-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000038.6(APC):c.4634C>G(p.Ser1545*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_000038.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 66
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Pathogenic:1
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. -
not provided Pathogenic:1
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Hereditary cancer-predisposing syndrome Pathogenic:1
The p.S1545* pathogenic mutation (also known as c.4634C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 4634. This changes the amino acid from a serine to a stop codon within coding exon 15. This alteration was identified in at least two unrelated patients with a clinical presentation of FAP or AFAP (Friedl W et al. Hered Cancer Clin Pract. 2005 Sep;3:95-114; Moisio AL et al. Gut. 2002 Jun;50:845-50). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at