FANCC

FA complementation group C, the group of FA core complex|FA complementation groups

Basic information

Region (hg38): 9:95099054-95426796

Previous symbols: [ "FACC" ]

Links

ENSG00000158169 ∙ NCBI:2176 ∙ OMIM:613899 ∙ HGNC:3584 ∙ Uniprot:Q00597 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fanconi anemia complementation group C (Definitive), mode of inheritance: AR
• Fanconi anemia complementation group C (Definitive), mode of inheritance: AR
• Fanconi anemia (Supportive), mode of inheritance: AR
• breast cancer (Limited), mode of inheritance: AD
• colorectal cancer (Limited), mode of inheritance: AD
• ovarian cancer (Limited), mode of inheritance: AD
• malignant pancreatic neoplasm (Limited), mode of inheritance: AD
• Fanconi anemia complementation group C (Definitive), mode of inheritance: AR
• Fanconi anemia complementation group C (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi anemia, complementation group C	AR	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Oncologic	Specific treatments can help manifestations (eg, oral androgens for blood counts; G-CSF for neutrophil count); HSCT can be curative, but solid tumor risk may remain; Surveillance for complications such as bone marrow failure is recommended; Fanconi anemia can involve congenital cardiac (and other) anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Allergy/Immunology/Infectious; Cardiovascular; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic; Renal	1574115; 9272737; 10431244; 20301575; 22160080; 22701786; 23028338

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FANCC gene.

• Fanconi anemia (69 variants)
• Hereditary cancer-predisposing syndrome (24 variants)
• Fanconi anemia complementation group C (19 variants)
• not provided (9 variants)
• Malignant tumor of breast (2 variants)
• Fanconi anemia complementation group A (2 variants)
• FANCC-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FANCC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	338	1	344
missense		3	671	17	2	693
nonsense	32	47	2			81
start loss		2				2
frameshift	48	59	5	1		113
inframe indel			17			17
splice donor/acceptor (+/-2bp)	6	49	4			59
splice region	1	1	35	63	1	101
non coding	1		70	233	33	337
Total	87	160	774	589	36

Highest pathogenic variant AF is 0.000210

Variants in FANCC

This is a list of pathogenic ClinVar variants found in the FANCC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-95099143-G-A		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099155-A-G		Fanconi anemia complementation group C	Benign (Jan 13, 2018)
9-95099179-T-C		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099183-C-T		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099305-C-G		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099399-C-T		Fanconi anemia complementation group C	Uncertain significance (Jan 12, 2018)
9-95099402-C-T		Fanconi anemia complementation group C	Uncertain significance (Jan 12, 2018)
9-95099411-C-T		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099436-C-T		Fanconi anemia complementation group C	Likely benign (Jan 12, 2018)
9-95099461-C-A		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099543-C-A		Fanconi anemia complementation group C	Uncertain significance (Apr 27, 2017)
9-95099543-C-T		Fanconi anemia complementation group C	Likely benign (Jan 13, 2018)
9-95099579-G-A		Fanconi anemia complementation group C	Uncertain significance (Jan 12, 2018)
9-95099622-G-T		Fanconi anemia complementation group C	Benign (Jan 12, 2018)
9-95099655-C-G		Fanconi anemia complementation group C	Uncertain significance (Jan 12, 2018)
9-95099731-G-A		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099739-C-T		Fanconi anemia complementation group C	Benign (Jan 13, 2018)
9-95099806-G-A		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099812-A-C		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099812-A-G		Fanconi anemia complementation group C	Likely benign (Jan 13, 2018)
9-95099828-G-A		Fanconi anemia complementation group C	Likely benign (Jan 13, 2018)
9-95099836-C-T		Fanconi anemia complementation group C	Benign (Jan 13, 2018)
9-95099980-A-G		Fanconi anemia complementation group C	Uncertain significance (Jan 13, 2018)
9-95099980-A-T		Fanconi anemia complementation group C	Benign (Apr 27, 2017)
9-95100032-T-C		Fanconi anemia complementation group C	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FANCC	protein_coding	protein_coding	ENST00000289081	14	218656

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.79e-13	0.429	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.194	306	297	1.03	0.0000161	3623
Missense in Polyphen		105	92.053	1.1407		1244
Synonymous	-0.722	122	112	1.09	0.00000665	1100
Loss of Function	1.36	24	32.3	0.742	0.00000166	350

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000627	0.000627
Ashkenazi Jewish	0.00	0.00
East Asian	0.000224	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000599	0.000598
Middle Eastern	0.000224	0.000217
South Asian	0.000360	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Upon IFNG induction, may facilitate STAT1 activation by recruiting STAT1 to IFNGR1. {ECO:0000269|PubMed:11520787}.
• Disease: DISEASE: Fanconi anemia complementation group C (FANCC) [MIM:227645]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. {ECO:0000269|PubMed:11520787, ECO:0000269|PubMed:15299030, ECO:0000269|PubMed:1574115, ECO:0000269|PubMed:8128956, ECO:0000269|PubMed:8499901, ECO:0000269|PubMed:8844212, ECO:0000269|PubMed:9242535}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);TP53 Regulates Transcription of DNA Repair Genes;Fanconi Anemia Pathway;DNA Repair;Gene expression (Transcription);role of brca1 brca2 and atr in cancer susceptibility;brca1 dependent ub ligase activity;Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 Regulates Transcription of DNA Repair Genes;Fanconi anemia pathway;Transcriptional Regulation by TP53;BARD1 signaling events (Consensus)

Recessive Scores

• pRec: 0.518

Intolerance Scores

• loftool: 0.951
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.58

Haploinsufficiency Scores

• pHI: 0.0746
• hipred: Y
• hipred_score: 0.518
• ghis: 0.482

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fancc
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; hematopoietic system phenotype; reproductive system phenotype

Gene ontology

• Biological process: myeloid cell homeostasis;DNA repair;nucleotide-excision repair;germ cell development;removal of superoxide radicals;cellular response to oxidative stress;interstrand cross-link repair;brain morphogenesis;protein-containing complex assembly;neuronal stem cell population maintenance
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;Fanconi anaemia nuclear complex
• Molecular function: protein binding