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NM_000136.3(FANCC):c.1009C>T (p.Leu337Phe) AND Fanconi anemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 15, 2015
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:
RCV000197177.1

Allele description

NM_000136.3(FANCC):c.1009C>T (p.Leu337Phe)

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.1009C>T (p.Leu337Phe)
Other names:
p.L337F:CTC>TTC
HGVS:
  • NC_000009.12:g.95117378G>A
  • NG_011707.1:g.205332C>T
  • NM_000136.3:c.1009C>TMANE SELECT
  • NM_001243743.2:c.1009C>T
  • NM_001243744.2:c.1009C>T
  • NP_000127.2:p.Leu337Phe
  • NP_001230672.1:p.Leu337Phe
  • NP_001230673.1:p.Leu337Phe
  • LRG_497t1:c.1009C>T
  • LRG_497:g.205332C>T
  • NC_000009.11:g.97879660G>A
  • NM_000136.2:c.1009C>T
Protein change:
L337F
Links:
dbSNP: rs587779899
NCBI 1000 Genomes Browser:
rs587779899
Molecular consequence:
  • NM_000136.3:c.1009C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243743.2:c.1009C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243744.2:c.1009C>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000254249Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 15, 2015) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000254249.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces leucine with phenylalanine at codon 337 of the FANCC protein (p.Leu337Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant has not been published in the literature and is present in population databases (no rs ID, <0.01%). ClinVar contains an entry for this variant (RCV000115340). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). However, the phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In summary, this is a rare missense change with uncertain impact on protein function. Although there is no indication that this variant causes disease, the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 8, 2022