NM_000038.6(APC):c.5240T>C (p.Met1747Thr) AND Familial adenomatous polyposis 1

delete

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 7, 2021
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:: RCV003534497.1

Allele description

NM_000038.6(APC):c.5240T>C (p.Met1747Thr)

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.5240T>C (p.Met1747Thr)

HGVS:

NC_000005.10:g.112840834T>C
NG_008481.4:g.153314T>C
NM_000038.6:c.5240T>CMANE SELECT
NM_001127510.3:c.5240T>C
NM_001127511.3:c.5186T>C
NM_001354895.2:c.5240T>C
NM_001354896.2:c.5294T>C
NM_001354897.2:c.5270T>C
NM_001354898.2:c.5165T>C
NM_001354899.2:c.5156T>C
NM_001354900.2:c.5117T>C
NM_001354901.2:c.5063T>C
NM_001354902.2:c.4967T>C
NM_001354903.2:c.4937T>C
NM_001354904.2:c.4862T>C
NM_001354905.2:c.4760T>C
NM_001354906.2:c.4391T>C
NP_000029.2:p.Met1747Thr
NP_001120982.1:p.Met1747Thr
NP_001120983.2:p.Met1729Thr
NP_001341824.1:p.Met1747Thr
NP_001341825.1:p.Met1765Thr
NP_001341826.1:p.Met1757Thr
NP_001341827.1:p.Met1722Thr
NP_001341828.1:p.Met1719Thr
NP_001341829.1:p.Met1706Thr
NP_001341830.1:p.Met1688Thr
NP_001341831.1:p.Met1656Thr
NP_001341832.1:p.Met1646Thr
NP_001341833.1:p.Met1621Thr
NP_001341834.1:p.Met1587Thr
NP_001341835.1:p.Met1464Thr
LRG_130:g.153314T>C
NC_000005.9:g.112176531T>C
NM_000038.5:c.5240T>C

Protein change:

M1464T

Links:

dbSNP: rs864622751

NCBI 1000 Genomes Browser:

rs864622751

Molecular consequence:

NM_000038.6:c.5240T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.5240T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.5186T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.5240T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.5294T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.5270T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.5165T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.5156T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.5117T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.5063T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.4967T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.4937T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.4862T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.4760T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.4391T>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000262296	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 7, 2021)	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

SCV000262296

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 7, 2021)

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, SCV000262296.7

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 221112). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 1747 of the APC protein (p.Met1747Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine.

#	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: Jun 2, 2024

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