NM_000038.6(APC):c.5939A>G (p.Asn1980Ser) AND Familial adenomatous polyposis 1

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Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 2, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003534872.1

Allele description

NM_000038.6(APC):c.5939A>G (p.Asn1980Ser)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.5939A>G (p.Asn1980Ser)

HGVS:

NC_000005.10:g.112841533A>G
NG_008481.4:g.154013A>G
NM_000038.6:c.5939A>GMANE SELECT
NM_001127510.3:c.5939A>G
NM_001127511.3:c.5885A>G
NM_001354895.2:c.5939A>G
NM_001354896.2:c.5993A>G
NM_001354897.2:c.5969A>G
NM_001354898.2:c.5864A>G
NM_001354899.2:c.5855A>G
NM_001354900.2:c.5816A>G
NM_001354901.2:c.5762A>G
NM_001354902.2:c.5666A>G
NM_001354903.2:c.5636A>G
NM_001354904.2:c.5561A>G
NM_001354905.2:c.5459A>G
NM_001354906.2:c.5090A>G
NM_001407446.1:c.6023A>G
NM_001407447.1:c.5993A>G
NM_001407448.1:c.5993A>G
NM_001407449.1:c.5993A>G
NM_001407450.1:c.5939A>G
NM_001407451.1:c.5918A>G
NM_001407452.1:c.5909A>G
NM_001407453.1:c.5762A>G
NM_001407454.1:c.5690A>G
NM_001407455.1:c.5690A>G
NM_001407456.1:c.5690A>G
NM_001407457.1:c.5690A>G
NM_001407458.1:c.5636A>G
NM_001407459.1:c.5636A>G
NM_001407460.1:c.5636A>G
NM_001407467.1:c.5552A>G
NM_001407469.1:c.5552A>G
NM_001407470.1:c.5090A>G
NM_001407471.1:c.4787A>G
NM_001407472.1:c.4787A>G
NP_000029.2:p.Asn1980Ser
NP_000029.2:p.Asn1980Ser
NP_001120982.1:p.Asn1980Ser
NP_001120982.1:p.Asn1980Ser
NP_001120983.1:p.Asn1980Ser
NP_001120983.2:p.Asn1962Ser
NP_001341824.1:p.Asn1980Ser
NP_001341825.1:p.Asn1998Ser
NP_001341826.1:p.Asn1990Ser
NP_001341827.1:p.Asn1955Ser
NP_001341828.1:p.Asn1952Ser
NP_001341829.1:p.Asn1939Ser
NP_001341830.1:p.Asn1921Ser
NP_001341831.1:p.Asn1889Ser
NP_001341832.1:p.Asn1879Ser
NP_001341833.1:p.Asn1854Ser
NP_001341834.1:p.Asn1820Ser
NP_001341835.1:p.Asn1697Ser
NP_001394375.1:p.Asn2008Ser
NP_001394376.1:p.Asn1998Ser
NP_001394377.1:p.Asn1998Ser
NP_001394378.1:p.Asn1998Ser
NP_001394379.1:p.Asn1980Ser
NP_001394380.1:p.Asn1973Ser
NP_001394381.1:p.Asn1970Ser
NP_001394382.1:p.Asn1921Ser
NP_001394383.1:p.Asn1897Ser
NP_001394384.1:p.Asn1897Ser
NP_001394385.1:p.Asn1897Ser
NP_001394386.1:p.Asn1897Ser
NP_001394387.1:p.Asn1879Ser
NP_001394388.1:p.Asn1879Ser
NP_001394389.1:p.Asn1879Ser
NP_001394396.1:p.Asn1851Ser
NP_001394398.1:p.Asn1851Ser
NP_001394399.1:p.Asn1697Ser
NP_001394400.1:p.Asn1596Ser
NP_001394401.1:p.Asn1596Ser
LRG_130t1:c.5939A>G
LRG_130t2:c.5939A>G
LRG_130t3:c.5939A>G
LRG_130:g.154013A>G
LRG_130p1:p.Asn1980Ser
LRG_130p2:p.Asn1980Ser
LRG_130p3:p.Asn1980Ser
NC_000005.9:g.112177230A>G
NM_000038.4:c.5939A>G
NM_000038.5:c.5939A>G
NM_001127510.1:c.5939A>G
NM_001127511.1:c.5939A>G
NR_176365.1:n.5774A>G
NR_176366.1:n.6193A>G

Protein change:

N1596S

Molecular consequence:

NM_000038.6:c.5939A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.5939A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.5885A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.5939A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.5993A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.5969A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.5864A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.5855A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.5816A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.5762A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.5666A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.5636A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.5561A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.5459A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.5090A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407446.1:c.6023A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407447.1:c.5993A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407448.1:c.5993A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407449.1:c.5993A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407450.1:c.5939A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407451.1:c.5918A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407452.1:c.5909A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407453.1:c.5762A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407454.1:c.5690A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407455.1:c.5690A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407456.1:c.5690A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407457.1:c.5690A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407458.1:c.5636A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407459.1:c.5636A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407460.1:c.5636A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407467.1:c.5552A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407469.1:c.5552A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407470.1:c.5090A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407471.1:c.4787A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407472.1:c.4787A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:: MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

Recent activity

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Chain A, ADP-ribosylation factor binding protein GGA1
Chain A, ADP-ribosylation factor binding protein GGA1
gi|29726571|pdb|1NAF|A

Protein
DC110311 Yamamoto/Hyodo-Miura NIBB/NBRP Xenopus DMZ pCS2p+ cDNA library Xenopus ...
DC110311 Yamamoto/Hyodo-Miura NIBB/NBRP Xenopus DMZ pCS2p+ cDNA library Xenopus laevis cDNA clone xl255b21 5', mRNA sequence
gi|119099682|gnl|dbEST|43369699|dbj 0311.1|

Nucleotide
Aortopulmonary collateral arteries
Aortopulmonary collateral arteries

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003299424	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 2, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003299424

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 2, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003299424.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1980 of the APC protein (p.Asn1980Ser). This variant is present in population databases (rs180727920, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1750604). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine