ZCCHC8

zinc finger CCHC-type containing 8, the group of Nuclear exosome targeting complex|Zinc fingers CCHC-type

Basic information

Region (hg38): 12:122471600-122500932

Links

ENSG00000033030 ∙ NCBI:55596 ∙ OMIM:616381 ∙ HGNC:25265 ∙ Uniprot:Q6NZY4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability (Limited), mode of inheritance: AR
• pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5	AD	Hematologic; Pulmonary	Surveillance and prompt treatment of bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, early recognition may allow prompt medical management	Hematologic; Pulmonary	31488579

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZCCHC8 gene.

• Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZCCHC8 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				70	4	74
missense		3	174	6	2	185
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)			1			1
splice region			8	10		18
non coding	1		10	37	5	53
Total	1	3	189	114	11

Variants in ZCCHC8

This is a list of pathogenic ClinVar variants found in the ZCCHC8 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-122473498-T-C			Likely benign (Dec 30, 2023)
12-122473500-T-C			Likely benign (Aug 04, 2023)
12-122473511-T-G		not specified	Uncertain significance (Jan 23, 2023)
12-122473528-T-A			Uncertain significance (Dec 19, 2023)
12-122473531-C-T		not specified	Uncertain significance (Jun 21, 2023)
12-122473533-G-A			Likely benign (Nov 04, 2022)
12-122473539-G-A			Likely benign (Jan 29, 2024)
12-122473548-C-T			Benign (Jan 31, 2024)
12-122473580-A-G			Uncertain significance (Apr 12, 2022)
12-122473609-G-A			Uncertain significance (Nov 28, 2023)
12-122473619-T-C		not specified	Uncertain significance (Dec 11, 2023)
12-122473621-G-A		not specified	Uncertain significance (Oct 15, 2023)
12-122473627-T-C		ZCCHC8-related disorder	Uncertain significance (Sep 15, 2023)
12-122473630-C-T			Uncertain significance (Nov 24, 2023)
12-122473634-T-C			Benign (Feb 01, 2024)
12-122473647-G-A		ZCCHC8-related disorder	Likely benign (Jul 19, 2022)
12-122473656-T-G			Uncertain significance (Sep 21, 2022)
12-122473657-T-C			Uncertain significance (Jun 14, 2023)
12-122473660-G-A			Uncertain significance (May 12, 2022)
12-122473665-C-A		ZCCHC8-related disorder	Likely benign (Nov 21, 2023)
12-122473665-C-T			Likely benign (Sep 09, 2022)
12-122473673-G-T			Uncertain significance (Feb 14, 2023)
12-122473680-G-A			Likely benign (Jul 07, 2023)
12-122473688-G-A			Uncertain significance (Jun 20, 2022)
12-122473689-A-G			Likely benign (Nov 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZCCHC8	protein_coding	protein_coding	ENST00000336229	14	28102

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.966	0.0342	124628	0	6	124634	0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.03	264	374	0.705	0.0000193	4614
Missense in Polyphen		61	112.33	0.54302		1437
Synonymous	1.51	119	142	0.839	0.00000822	1308
Loss of Function	4.47	5	32.5	0.154	0.00000169	398

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000646	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000455	0.0000442
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that directs a subset of non- coding short-lived RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484). May be involved in pre-mRNA splicing (Probable). {ECO:0000269|PubMed:27871484, ECO:0000305|PubMed:16263084}.

Recessive Scores

• pRec: 0.0931

Haploinsufficiency Scores

• pHI: 0.346
• hipred: N
• hipred_score: 0.491
• ghis: 0.555

Essentials

• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zcchc8

Gene ontology

• Biological process: mRNA splicing, via spliceosome
• Cellular component: nucleus;nucleoplasm;nucleolus;nuclear body;TRAMP complex;catalytic step 2 spliceosome
• Molecular function: RNA binding;protein binding;zinc ion binding