NM_000136.3(FANCC):c.1368G>T (p.Met456Ile) AND Fanconi anemia

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 17, 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:: RCV000199855.10

Allele description [Variation Report for NM_000136.3(FANCC):c.1368G>T (p.Met456Ile)]

NM_000136.3(FANCC):c.1368G>T (p.Met456Ile)

Genes:

FANCC:FA complementation group C [Gene - OMIM - HGNC]
AOPEP:aminopeptidase O (putative) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.1368G>T (p.Met456Ile)

HGVS:

NC_000009.12:g.95107231C>A
NG_011707.1:g.215479G>T
NM_000136.3:c.1368G>TMANE SELECT
NM_001243743.2:c.1368G>T
NP_000127.2:p.Met456Ile
NP_001230672.1:p.Met456Ile
LRG_497t1:c.1368G>T
LRG_497:g.215479G>T
NC_000009.11:g.97869513C>A
NM_000136.2:c.1368G>T

Protein change:

M456I

Links:

dbSNP: rs863224609

NCBI 1000 Genomes Browser:

rs863224609

Molecular consequence:

NM_000136.3:c.1368G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243743.2:c.1368G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

Recent activity

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ATP synthase F0 subunit 8 (mitochondrion) [Cacatua moluccensis]
ATP synthase F0 subunit 8 (mitochondrion) [Cacatua moluccensis]
gi|470226826|ref|YP_007624583.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000254253	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002081150	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 28, 2018)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000254253

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 17, 2021)

germline

clinical testing

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

SCV002081150

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 28, 2018)

germline

clinical testing

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000254253.6

#	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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 216283). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 456 of the FANCC protein (p.Met456Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine.

#	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

From Natera, Inc., SCV002081150.1

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

#	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: Sep 29, 2024

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