TSEN34

tRNA splicing endonuclease subunit 34, the group of tRNA-splicing endonuclease subunits

Basic information

Region (hg38): 19:54189937-54194536

Previous symbols: [ "LENG5" ]

Links

ENSG00000170892 ∙ NCBI:79042 ∙ OMIM:608754 ∙ HGNC:15506 ∙ Uniprot:Q9BSV6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 2C (Limited), mode of inheritance: AR
• pontocerebellar hypoplasia type 2C (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 2 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 2C (Limited), mode of inheritance: AR
• pontocerebellar hypoplasia type 2C (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 2C	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	18711368

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TSEN34 gene.

• not provided (76 variants)
• Pontoneocerebellar hypoplasia (60 variants)
• not specified (19 variants)
• Inborn genetic diseases (13 variants)
• Pontocerebellar hypoplasia type 2C (3 variants)
• Intellectual disability, autosomal recessive 57 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TSEN34 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			9	14	2	25
missense			35	4	1	40
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region					1	1
non coding			20	19	21	60
Total	0	1	66	37	24

Variants in TSEN34

This is a list of pathogenic ClinVar variants found in the TSEN34 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-54190237-C-T			Benign (Feb 24, 2021)
19-54190280-C-A		Pontoneocerebellar hypoplasia	Uncertain significance (Jun 14, 2016)
19-54190360-A-G		Pontoneocerebellar hypoplasia	Likely benign (Jan 13, 2018)
19-54190414-G-A		Pontoneocerebellar hypoplasia	Uncertain significance (Jan 12, 2018)
19-54190465-G-A		Pontoneocerebellar hypoplasia • not specified	Likely benign (Jan 13, 2018)
19-54190483-G-C			Benign (Jan 28, 2020)
19-54190699-A-A			Benign (Jan 28, 2020)
19-54190921-G-C		Intellectual disability, autosomal recessive 57	Likely benign (Nov 19, 2021)
19-54191122-A-A			Benign (Jun 26, 2018)
19-54191164-C-G			Benign (Jun 26, 2018)
19-54191191-G-C			Likely benign (May 14, 2019)
19-54191203-G-T			Likely benign (Jul 11, 2018)
19-54191226-C-T			Likely benign (Feb 05, 2019)
19-54191295-G-A			Likely benign (Jun 16, 2018)
19-54191312-C-C			Benign (Jun 26, 2018)
19-54191332-G-C		not specified	Likely benign (-)
19-54191356-C-T		not specified	Likely benign (Oct 10, 2016)
19-54191357-G-A		not specified	Conflicting classifications of pathogenicity (Jul 21, 2017)
19-54191369-T-C		Pontoneocerebellar hypoplasia	Uncertain significance (Feb 08, 2023)
19-54191402-T-C		not specified	Uncertain significance (Jul 26, 2022)
19-54191403-G-A		not specified • Pontoneocerebellar hypoplasia	Benign/Likely benign (Oct 13, 2023)
19-54191437-C-T		Pontoneocerebellar hypoplasia	Uncertain significance (Jan 13, 2018)
19-54191454-C-T			Likely benign (Jun 22, 2023)
19-54191458-A-C		not specified	Uncertain significance (Dec 21, 2021)
19-54191459-C-A		Pontoneocerebellar hypoplasia	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TSEN34	protein_coding	protein_coding	ENST00000396383	4	3797

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.361	0.636	124791	0	11	124802	0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.965	217	181	1.20	0.0000104	1938
Missense in Polyphen		63	66.509	0.94725		684
Synonymous	-1.93	103	80.9	1.27	0.00000474	687
Loss of Function	2.61	3	13.3	0.226	7.38e-7	132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000497	0.000497
East Asian	0.0000556	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000451	0.0000441
Middle Eastern	0.0000556	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constitutes one of the two 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. 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. It probably carries the active site for 3'-splice site cleavage. 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. {ECO:0000269|PubMed:15109492}.
• Disease: DISEASE: Pontocerebellar hypoplasia 2C (PCH2C) [MIM:612390]: A disorder characterized by an abnormally small cerebellum and brainstem, and progressive microcephaly from birth combined with extrapyramidal dyskinesia. Severe chorea occurs and epilepsy is frequent. There are no signs of spinal cord anterior horn cells degeneration. {ECO:0000269|PubMed:18711368}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: tRNA processing;Metabolism of RNA;tRNA processing in the nucleus;tRNA splicing (Consensus)

Recessive Scores

• pRec: 0.0906

Intolerance Scores

• loftool: 0.430
• rvis_EVS: 0.08
• rvis_percentile_EVS: 60.09

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.283
• ghis: 0.521

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.710

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tsen34

Gene ontology

• Biological process: tRNA-type intron splice site recognition and cleavage;mRNA processing;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: tRNA-intron endonuclease complex;nucleus;nucleoplasm;nucleolus
• Molecular function: tRNA-intron endonuclease activity;nucleic acid binding;lyase activity