Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000038.6(APC):c.1409-3T>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA658655932

485146 (ClinVar)

Gene: APC

Condition: familial adenomatous polyposis 1

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: daf56198-abfb-4fa3-8081-4503570751dc

Approved on: 2025-05-16

Published on: 2025-05-16

HGVS expressions

NM_000038.6:c.1409-3T>G

NM_000038.6(APC):c.1409-3T>G

NC_000005.10:g.112827105T>G

CM000667.2:g.112827105T>G

NC_000005.9:g.112162802T>G

CM000667.1:g.112162802T>G

NC_000005.8:g.112190701T>G

NG_008481.4:g.139585T>G

ENST00000502371.3:c.1408+5114T>G

ENST00000504915.3:c.1463-3T>G

ENST00000505084.2:n.1465-3T>G

ENST00000505350.2:c.*1415-3T>G

ENST00000507379.6:c.1355-3T>G

ENST00000509732.6:c.1409-3T>G

ENST00000512211.7:c.1409-3T>G

ENST00000257430.9:c.1409-3T>G

ENST00000257430.8:c.1409-3T>G

ENST00000502371.2:c.96+5114T>G

ENST00000504915.2:c.98-3T>G

ENST00000507379.5:c.1355-3T>G

ENST00000508376.6:c.1409-3T>G

ENST00000508624.5:c.*731-3T>G

ENST00000512211.6:c.1409-3T>G

NM_000038.5:c.1409-3T>G

NM_001127510.2:c.1409-3T>G

NM_001127511.2:c.1355-3T>G

NM_001354895.1:c.1409-3T>G

NM_001354896.1:c.1463-3T>G

NM_001354897.1:c.1439-3T>G

NM_001354898.1:c.1334-3T>G

NM_001354899.1:c.1325-3T>G

NM_001354900.1:c.1286-3T>G

NM_001354901.1:c.1232-3T>G

NM_001354902.1:c.1136-3T>G

NM_001354903.1:c.1106-3T>G

NM_001354904.1:c.1031-3T>G

NM_001354905.1:c.929-3T>G

NM_001354906.1:c.560-3T>G

NM_001127510.3:c.1409-3T>G

NM_001127511.3:c.1355-3T>G

NM_001354895.2:c.1409-3T>G

NM_001354896.2:c.1463-3T>G

NM_001354897.2:c.1439-3T>G

NM_001354898.2:c.1334-3T>G

NM_001354899.2:c.1325-3T>G

NM_001354900.2:c.1286-3T>G

NM_001354901.2:c.1232-3T>G

NM_001354902.2:c.1136-3T>G

NM_001354903.2:c.1106-3T>G

NM_001354904.2:c.1031-3T>G

NM_001354905.2:c.929-3T>G

NM_001354906.2:c.560-3T>G

Likely Pathogenic

PS3_Moderate PP3 PM2_Supporting PS4_Moderate

Evidence Links 1

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for APC Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The NM_000038.6(APC):c.1409-3T>G variant in APC is an intronic variant which is located at the 3rd nucleotide upstream of exon 12. This variant has been reported in 4 probands meeting phenotypic criteria resulting in a total phenotype score of 2.0 points (PS4_Moderate, internal data Ambry Genetics and Labcorp Genetics [formerly Invitae], PMID: 20685668). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The results from ≥ 2 in silico splicing predictors (SpliceAI and VarSeak) indicate that this variant may affect splicing by disrupting the acceptor site of intron 11 of APC and/or by creating a strong alternate acceptor (PP3). Mini-gene assay demonstrated that the variant impacts splicing by skipping of exon 12 resulting in a frameshift and premature termination (PS3_Moderate, PMID: 20685668). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal-dominant inherited FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: criteria PS3_Moderate, PS4_Moderate, PM2_Supporting and PP3 applied (VCEP specifications version 2.0.3; date of approval: 7/24/2023).

PS3_Moderate

Mini-gene assay demonstrated that the variant impacts splicing by skipping of exon 12 resulting in a frameshift and premature termination (PS3_Moderate, PMID: 20685668).

Mini-gene assay PubMed:20685668

PP3

The results from ≥ 2 in silico splicing predictors (SpliceAI and VarSeak) indicate that this variant may affect splicing by disrupting the acceptor site of intron 11 of APC and/or by creating a strong alternate acceptor (PP3).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PS4_Moderate

This variant has been reported in 4 probands meeting phenotypic criteria resulting in a total phenotype score of 2.0 points (PS4_Moderate, internal data Ambry Genetics and Labcorp Genetics [formerly Invitae], PMID: 20685668).

Curation History

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