chr5-112801308-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7
The NM_000038.6(APC):c.759C>G(p.Gly253=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,910 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). Synonymous variant affecting the same amino acid position (i.e. G253G) has been classified as Likely benign.
Frequency
Consequence
NM_000038.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APC | NM_000038.6 | c.759C>G | p.Gly253= | synonymous_variant | 8/16 | ENST00000257430.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APC | ENST00000257430.9 | c.759C>G | p.Gly253= | synonymous_variant | 8/16 | 5 | NM_000038.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250946Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135598
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1460732Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 726644
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 1 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 26, 2024 | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. - |
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 18, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 15, 2014 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 21, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge - |
APC-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 06, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at