CWC27

CWC27 spliceosome associated cyclophilin, the group of Cyclophilin peptidylprolyl isomerases|Spliceosomal C complex|Spliceosomal Bact complex|Spliceosomal P complex|NTC associated proteins

Basic information

Region (hg38): 5:64766368-65102412

Previous symbols: [ "SDCCAG10" ]

Links

ENSG00000153015 ∙ NCBI:10283 ∙ OMIM:617170 ∙ HGNC:10664 ∙ Uniprot:Q6UX04 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (Strong), mode of inheritance: AR
• metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa with or without skeletal anomalies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	28285769

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CWC27 gene.

• not provided (23 variants)
• Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CWC27 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			3	50	3	56
missense			134	2	2	138
nonsense	8				1	9
start loss						0
frameshift	14	1	2			17
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	8				9
splice region	1		10	21	6	38
non coding				54	13	67
Total	23	9	141	106	19

Highest pathogenic variant AF is 0.0000197

Variants in CWC27

This is a list of pathogenic ClinVar variants found in the CWC27 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-64769116-G-A		Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome	Benign (Jul 30, 2021)
5-64769156-A-G			Uncertain significance (Dec 18, 2023)
5-64769160-ACATC-A			Pathogenic (Aug 10, 2022)
5-64769162-A-G			Uncertain significance (Aug 09, 2022)
5-64769166-A-C			Uncertain significance (Jul 17, 2023)
5-64769178-C-T			Uncertain significance (Jul 05, 2022)
5-64769179-G-A			Likely benign (Jul 03, 2022)
5-64769189-G-A			Likely pathogenic (Feb 27, 2022)
5-64769196-C-T			Likely benign (Dec 12, 2021)
5-64769204-A-G			Likely benign (Feb 24, 2022)
5-64774673-G-T			Likely benign (May 27, 2022)
5-64774691-G-A			Uncertain significance (Nov 01, 2022)
5-64774697-T-C		CWC27-related disorder	Likely benign (Dec 26, 2023)
5-64774701-A-G			Uncertain significance (Jul 06, 2022)
5-64774704-C-G			Uncertain significance (Jun 05, 2022)
5-64774708-A-C			Likely benign (Jan 21, 2024)
5-64774719-T-C			Uncertain significance (Oct 04, 2021)
5-64774723-CAT-C			Pathogenic (Jul 26, 2022)
5-64774724-A-C			Uncertain significance (Jun 04, 2022)
5-64774734-G-C		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
5-64774742-G-T			Pathogenic (Aug 09, 2022)
5-64774747-T-C			Likely benign (Jan 09, 2024)
5-64774748-C-A			Uncertain significance (Jul 21, 2022)
5-64774748-C-T			Uncertain significance (Jul 19, 2022)
5-64774764-A-AT			Pathogenic (Nov 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CWC27	protein_coding	protein_coding	ENST00000381070	14	249834

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.56e-7	0.958	125710	0	38	125748	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.762	193	225	0.857	0.0000113	3109
Missense in Polyphen		60	82.088	0.73092		1096
Synonymous	1.41	60	75.6	0.793	0.00000369	802
Loss of Function	1.94	14	24.4	0.575	0.00000114	360

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000578	0.000562
Ashkenazi Jewish	0.00	0.00
East Asian	0.000225	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000171	0.000167
Middle Eastern	0.000225	0.000217
South Asian	0.0000681	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As part of the spliceosome, plays a role in pre-mRNA splicing (PubMed:29360106). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357). {ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:29360106}.
• Disease: DISEASE: Retinitis pigmentosa with or without skeletal anomalies (RPSKA) [MIM:250410]: An autosomal recessive disease characterized by retinal degeneration, brachydactyly, short stature, craniofacial dysmorphism, and neurologic defects. Retinal defects are consistent with retinitis pigmentosa in most patients. Neurologic manifestations include mild-to-moderate intellectual disability and psychomotor retardation. {ECO:0000269|PubMed:28285769}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Intolerance Scores

• loftool: 0.843
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• pHI: 0.0721
• hipred: N
• hipred_score: 0.436
• ghis: 0.613

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.283

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cwc27
• Phenotype: reproductive 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: mRNA splicing, via spliceosome;protein peptidyl-prolyl isomerization;protein folding
• Cellular component: nucleus;nucleoplasm;catalytic step 1 spliceosome;catalytic step 2 spliceosome
• Molecular function: peptidyl-prolyl cis-trans isomerase activity;cyclosporin A binding