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NM_000136.3(FANCC):c.29G>A (p.Cys10Tyr) AND Fanconi anemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 3, 2022
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:
RCV000233348.11

Allele description [Variation Report for NM_000136.3(FANCC):c.29G>A (p.Cys10Tyr)]

NM_000136.3(FANCC):c.29G>A (p.Cys10Tyr)

Gene:
FANCC:FA complementation group C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.32
Genomic location:
Preferred name:
NM_000136.3(FANCC):c.29G>A (p.Cys10Tyr)
Other names:
p.C10Y:TGT>TAT
HGVS:
  • NC_000009.12:g.95249263C>T
  • NG_011707.1:g.73447G>A
  • NM_000136.3:c.29G>AMANE SELECT
  • NM_001243743.2:c.29G>A
  • NM_001243744.2:c.29G>A
  • NP_000127.2:p.Cys10Tyr
  • NP_001230672.1:p.Cys10Tyr
  • NP_001230673.1:p.Cys10Tyr
  • LRG_497t1:c.29G>A
  • LRG_497:g.73447G>A
  • NC_000009.11:g.98011545C>T
  • NM_000136.2:c.29G>A
Protein change:
C10Y
Links:
dbSNP: rs143152201
NCBI 1000 Genomes Browser:
rs143152201
Molecular consequence:
  • NM_000136.3:c.29G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243743.2:c.29G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243744.2:c.29G>A - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000283589Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Nov 3, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Patterns and functional implications of rare germline variants across 12 cancer types.

Lu C, Xie M, Wendl MC, Wang J, McLellan MD, Leiserson MD, Huang KL, Wyczalkowski MA, Jayasinghe R, Banerjee T, Ning J, Tripathi P, Zhang Q, Niu B, Ye K, Schmidt HK, Fulton RS, McMichael JF, Batra P, Kandoth C, Bharadwaj M, Koboldt DC, et al.

Nat Commun. 2015 Dec 22;6:10086. doi: 10.1038/ncomms10086.

PubMed [citation]
PMID:
26689913
PMCID:
PMC4703835

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, SCV000283589.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 10 of the FANCC protein (p.Cys10Tyr). This variant is present in population databases (rs143152201, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with breast cancer (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 127538). 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 FANCC protein function. 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.

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

Last Updated: Jan 19, 2025