ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.311C>G (p.Ser104Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000038.6(APC):c.311C>G (p.Ser104Ter)
Variation ID: 231513 Accession: VCV000231513.21
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 5q22.2 5: 112767279 (GRCh38) [ NCBI UCSC ] 5: 112102976 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Sep 30, 2017 Feb 14, 2024 Nov 6, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000038.6:c.311C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Ser104Ter nonsense NM_001127510.3:c.311C>G NP_001120982.1:p.Ser104Ter nonsense NM_001127511.3:c.341C>G NP_001120983.2:p.Ser114Ter nonsense NM_001354895.2:c.311C>G NP_001341824.1:p.Ser104Ter nonsense NM_001354896.2:c.311C>G NP_001341825.1:p.Ser104Ter nonsense NM_001354897.2:c.341C>G NP_001341826.1:p.Ser114Ter nonsense NM_001354898.2:c.236C>G NP_001341827.1:p.Ser79Ter nonsense NM_001354899.2:c.311C>G NP_001341828.1:p.Ser104Ter nonsense NM_001354900.2:c.134C>G NP_001341829.1:p.Ser45Ter nonsense NM_001354901.2:c.134C>G NP_001341830.1:p.Ser45Ter nonsense NM_001354902.2:c.341C>G NP_001341831.1:p.Ser114Ter nonsense NM_001354903.2:c.311C>G NP_001341832.1:p.Ser104Ter nonsense NM_001354904.2:c.236C>G NP_001341833.1:p.Ser79Ter nonsense NM_001354905.2:c.134C>G NP_001341834.1:p.Ser45Ter nonsense NM_001354906.2:c.-725C>G 5 prime UTR NC_000005.10:g.112767279C>G NC_000005.9:g.112102976C>G NG_008481.4:g.79759C>G LRG_130:g.79759C>G - Protein change
- S104*, S114*, S79*, S45*
- Other names
- -
- Canonical SPDI
- NC_000005.10:112767278:C:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13997 | 14130 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (1) |
criteria provided, single submitter
|
Aug 14, 2021 | RCV000213087.10 | |
Pathogenic (1) |
criteria provided, single submitter
|
Mar 5, 2017 | RCV000506152.15 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Mar 10, 2017 | RCV000519665.8 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 14, 2022 | RCV001254064.12 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 6, 2023 | RCV003335254.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Mar 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602536.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
|
|
Likely pathogenic
(Mar 10, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000617331.2
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Comment:
This variant is denoted APC c.311C>G at the cDNA level and p.Ser104Ter (S104X) at the protein level. The substitution creates a nonsense variant, which changes … (more)
This variant is denoted APC c.311C>G at the cDNA level and p.Ser104Ter (S104X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA). While this variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, Heppner Gross (2002) has demonstrated the production of a functional truncated APC protein, although at a low level, through the use of an alternate downstream Methionine codon. This variant has been reported in at least one individual with a personal and/or family history suggestive of Familial Adenomatous Polyposis (Garzon-Benavides 2010). Based on the currently available information, we consider this variant to be likely pathogenic. (less)
|
|
Pathogenic
(Oct 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München
Accession: SCV001429974.1
First in ClinVar: Aug 21, 2020 Last updated: Aug 21, 2020 |
Clinical Features:
Flexion contracture of finger (present) , Macrocephaly (present) , Long philtrum (present) , Poor suck (present) , Low-set ears (present) , Knee flexion contracture (present) … (more)
Flexion contracture of finger (present) , Macrocephaly (present) , Long philtrum (present) , Poor suck (present) , Low-set ears (present) , Knee flexion contracture (present) , Narrow mouth (present) , Cryptorchidism (present) , Retrognathia (present) , Aplasia/Hypoplasia involving bones of the thorax (present) , Micrognathia (present) , Hypertelorism (present) , Respiratory failure (present) (less)
Sex: male
Tissue: blood
|
|
Pathogenic
(Aug 14, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000275387.6
First in ClinVar: May 29, 2016 Last updated: Nov 29, 2022 |
Comment:
The p.S104* pathogenic mutation (also known as c.311C>G), located in coding exon 3 of the APC gene, results from a C to G substitution at … (more)
The p.S104* pathogenic mutation (also known as c.311C>G), located in coding exon 3 of the APC gene, results from a C to G substitution at nucleotide position 311. This changes the amino acid from a serine to a stop codon within coding exon 3. This mutation has been detected in multiple individuals with a personal and/or family history of polyposis (Garzón-Benavides M et al. Rev Esp Enferm Dig, 2010 Nov;102:653-7; Ambry internal data). In a cohort of 300 deceased patients who underwent whole genome sequencing for 60 autosomal dominant cancer predisposition genes, this variant was detected and classified as likely pathogenic by the authors. However, the specific phenotype of the patient with this alteration was not reported (He KY et al. PLoS One, 2016 Dec;11:e0167847). 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. (less)
Number of individuals with the variant: 1
|
|
Pathogenic
(Apr 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004044782.2
First in ClinVar: Oct 21, 2023 Last updated: Oct 28, 2023 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
|
|
Pathogenic
(Nov 14, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004207339.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Nov 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002232943.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Ser104*) in the APC gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Ser104*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of familial adenomatous polyposis (PMID: 21142386). ClinVar contains an entry for this variant (Variation ID: 231513). For these reasons, this variant has been classified as Pathogenic. (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records. | He KY | PloS one | 2016 | PMID: 27930734 |
Andalusian Registry for familial adenomatous polyposis. Analysis of patients included. | Garzón-Benavides M | Revista espanola de enfermedades digestivas | 2010 | PMID: 21142386 |
Germline APC mutation spectrum derived from 863 genomic variations identified through a 15-year medical genetics service to French patients with FAP. | Lagarde A | Journal of medical genetics | 2010 | PMID: 20685668 |
Mutational screening of the APC gene in Chilean families with familial adenomatous polyposis: nine novel truncating mutations. | De la Fuente MK | Diseases of the colon and rectum | 2007 | PMID: 17963004 |
Text-mined citations for rs74953290 ...
HelpRecord last updated Mar 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.