XRCC3
Basic information
Region (hg38): 14:103697608-103715504
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRCC3 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 | 4 | |||||
missense | 30 | 39 | ||||
nonsense | 1 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region ? | 0 | |||||
non coding ? | 1 | |||||
Total | 0 | 0 | 31 | 6 | 8 |
Variants in XRCC3
This is a list of pathogenic ClinVar variants found in the XRCC3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
14-103698819-T-G | XRCC3-related disorder | Likely benign (Jul 10, 2019) | ||
14-103698827-G-A | Familial cancer of breast | Uncertain significance (Jul 06, 2022) | ||
14-103698901-C-T | not specified | Uncertain significance (Jan 23, 2024) | ||
14-103698914-C-T | Ovarian cancer | Benign (Jan 01, 2022) | ||
14-103698934-C-T | XRCC3-related disorder | Likely benign (Jun 11, 2019) | ||
14-103698935-G-A | not specified | Uncertain significance (Mar 23, 2022) | ||
14-103698941-G-A | not specified | Uncertain significance (Jul 06, 2021) | ||
14-103699003-C-T | not specified | Uncertain significance (Dec 14, 2023) | ||
14-103699007-C-T | not specified | Uncertain significance (Jun 24, 2022) | ||
14-103699010-C-A | not specified | Uncertain significance (Oct 12, 2022) | ||
14-103699143-C-T | Ovarian cancer | Benign (Jan 01, 2022) | ||
14-103699152-C-T | not specified | Uncertain significance (Jul 05, 2023) | ||
14-103699153-G-A | XRCC3-related disorder | Likely benign (Aug 14, 2019) | ||
14-103699161-C-T | not specified | Uncertain significance (Mar 23, 2022) | ||
14-103699345-A-C | Benign (Dec 07, 2023) | |||
14-103699410-C-T | Benign (Mar 29, 2018) | |||
14-103699411-G-A | not specified | Uncertain significance (May 24, 2023) | ||
14-103699416-G-A | Melanoma, cutaneous malignant, susceptibility to, 6 • XRCC3-related disorder | Benign (Sep 08, 2023) | ||
14-103699453-C-T | not specified | Uncertain significance (Jan 19, 2024) | ||
14-103699469-A-C | not specified | Uncertain significance (Nov 09, 2022) | ||
14-103699472-T-G | not specified | Uncertain significance (Dec 08, 2023) | ||
14-103699479-C-T | not specified | Uncertain significance (Jul 06, 2021) | ||
14-103699515-C-T | not specified | Uncertain significance (May 31, 2023) | ||
14-103699521-A-C | not specified | Uncertain significance (Oct 03, 2023) | ||
14-103699558-C-T | not specified | Uncertain significance (Jun 17, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
XRCC3 | protein_coding | protein_coding | ENST00000553264 | 7 | 17896 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.91e-10 | 0.0354 | 125721 | 0 | 17 | 125738 | 0.0000676 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.386 | 192 | 208 | 0.925 | 0.0000153 | 2136 |
Missense in Polyphen | 54 | 58.865 | 0.91735 | 593 | ||
Synonymous | -0.462 | 103 | 97.2 | 1.06 | 0.00000739 | 742 |
Loss of Function | -0.425 | 14 | 12.4 | 1.13 | 6.28e-7 | 142 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0000918 | 0.0000916 |
Ashkenazi Jewish | 0.0000993 | 0.0000992 |
East Asian | 0.00 | 0.00 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.0000707 | 0.0000703 |
Middle Eastern | 0.00 | 0.00 |
South Asian | 0.000196 | 0.000196 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD21 paralog protein complex CX3 which acts in the BRCA1-BRCA2- dependent HR pathway. Upon DNA damage, CX3 acts downstream of RAD51 recruitment; the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. Involved in HJ resolution and thus in processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex and seems to involve GEN1 during mitotic cell cycle progression. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C. {ECO:0000269|PubMed:14716019, ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23108668, ECO:0000269|PubMed:23149936}.;
- Disease
- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:12023982}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Melanoma, cutaneous malignant 6 (CMM6) [MIM:613972]: A malignant neoplasm of melanocytes, arising de novo or from a pre- existing benign nevus, which occurs most often in the skin but also may involve other sites. {ECO:0000269|PubMed:11059748}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Fluoropyrimidine Pathway, Pharmacodynamics;Homologous recombination - Homo sapiens (human);Fluoropyrimidine Activity;Integrated Breast Cancer Pathway;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Fanconi anemia pathway;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR)
(Consensus)
Recessive Scores
- pRec
- 0.405
Intolerance Scores
- loftool
- 0.671
- rvis_EVS
- 0.24
- rvis_percentile_EVS
- 69.37
Haploinsufficiency Scores
- pHI
- 0.632
- hipred
- N
- hipred_score
- 0.458
- ghis
- 0.539
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.974
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Xrcc3
- Phenotype
- hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype;
Gene ontology
- Biological process
- telomere maintenance via recombination;double-strand break repair via homologous recombination;DNA repair;DNA recombination;cellular response to DNA damage stimulus;response to organic substance;regulation of centrosome duplication;interstrand cross-link repair;double-strand break repair via synthesis-dependent strand annealing;resolution of mitotic recombination intermediates;positive regulation of mitotic cell cycle spindle assembly checkpoint;t-circle formation;telomeric loop disassembly;telomere maintenance via telomere trimming
- Cellular component
- nuclear chromosome, telomeric region;nucleus;nucleoplasm;replication fork;cytoplasm;mitochondrion;cytosol;Rad51C-XRCC3 complex;perinuclear region of cytoplasm
- Molecular function
- four-way junction DNA binding;protein binding;ATP binding;DNA-dependent ATPase activity;crossover junction endodeoxyribonuclease activity