TSEN15

tRNA splicing endonuclease subunit 15, the group of tRNA-splicing endonuclease subunits

Basic information

Region (hg38): 1:184051651-184123978

Previous symbols: [ "C1orf19" ]

Links

ENSG00000198860 ∙ NCBI:116461 ∙ OMIM:608756 ∙ HGNC:16791 ∙ Uniprot:Q8WW01 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 2 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia, type 2F (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia, type 2F (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia, type 2F (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia type 2F	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	Neurologic	25558065; 2739207

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TSEN15 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSEN15 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				2		2
missense		1	21		2	24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				7	9	16
Total	0	1	21	9	11

Variants in TSEN15

This is a list of pathogenic ClinVar variants found in the TSEN15 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-184051687-G-A			Benign (May 19, 2019)
1-184051715-C-A			Benign (Aug 14, 2018)
1-184051751-C-T		TSEN15-related disorder	Likely benign (May 23, 2019)
1-184051768-G-A		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
1-184051777-G-C		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
1-184051783-A-G		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
1-184051786-C-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
1-184051791-C-T			Likely benign (Dec 04, 2020)
1-184051795-A-G		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
1-184051801-C-A		TSEN15-related disorder	Likely benign (Oct 11, 2022)
1-184051811-G-A		not specified	Benign (Jul 15, 2018)
1-184051816-G-C		Inborn genetic diseases	Uncertain significance (Aug 10, 2024)
1-184051822-G-C		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
1-184051831-G-T		Inborn genetic diseases	Uncertain significance (Sep 19, 2022)
1-184051840-G-A		Inborn genetic diseases	Uncertain significance (May 14, 2021)
1-184051894-A-T		Inborn genetic diseases	Uncertain significance (Mar 27, 2024)
1-184051999-C-T			Likely benign (Nov 27, 2018)
1-184052187-G-A			Likely benign (Sep 18, 2018)
1-184054364-T-C		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
1-184054395-A-C		not specified	Benign (Jul 15, 2018)
1-184054407-G-A		TSEN15-related disorder	Likely benign (Dec 16, 2019)
1-184054410-C-G		Pontocerebellar hypoplasia, type 2F	Uncertain significance (Mar 11, 2024)
1-184054533-T-C			Likely benign (Nov 27, 2018)
1-184054712-A-G			Benign (Dec 23, 2018)
1-184054736-T-G		Seizure;Global developmental delay;Primary microcephaly • Pontocerebellar hypoplasia, type 2F	Uncertain significance (Mar 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSEN15	protein_coding	protein_coding	ENST00000361641	5	22536

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.279	0.700	125722	0	6	125728	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.17	56	86.7	0.646	0.00000400	1097
Missense in Polyphen		11	27.752	0.39636		350
Synonymous	0.918	25	31.6	0.792	0.00000157	333
Loss of Function	1.95	2	7.91	0.253	4.00e-7	99

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000907	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non-catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5' and 3' splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-OH termini (PubMed:15109492, PubMed:27392077). There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre- mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events (PubMed:15109492). {ECO:0000269|PubMed:15109492, ECO:0000269|PubMed:27392077}.
• Pathway: tRNA processing;Metabolism of RNA;tRNA processing in the nucleus;tRNA splicing (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.537
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.57

Haploinsufficiency Scores

• pHI: 0.159
• hipred: N
• hipred_score: 0.338
• ghis: 0.417

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.650

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tsen15

Gene ontology

• Biological process: tRNA splicing, via endonucleolytic cleavage and ligation;mRNA processing;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: nucleoplasm;nucleolus
• Molecular function: tRNA-intron endonuclease activity;nucleic acid binding