TSEN15

Chr 1AR

tRNA splicing endonuclease subunit 15

Also known as: C1orf19, PCH2F, sen15

NCBI Gene: 116461 ENSG00000198860 UniProt: Q8WW01 OMIM: 608756

The protein is a subunit of the tRNA splicing endonuclease that catalyzes the removal of introns from tRNA precursors. Autosomal recessive mutations cause pontocerebellar hypoplasia type 2F. Loss of function disrupts tRNA processing, which impairs protein synthesis and leads to the characteristic developmental abnormalities of the brainstem and cerebellum.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of the tRNA splicing endonuclease, which catalyzes the removal of introns from tRNA precursors. Alternative splicing results in multiple transcript variants. There is a pseudogene of this gene on chromosome 17. [provided by RefSeq, Jul 2014]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.801 OMIM phenotype

Clinical Summary— TSEN15

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 31 VUS of 67 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.279

Z-score 1.95

OE 0.25 (0.10–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.17Z-score

OE missense 0.65 (0.52–0.81)

56 obs / 86.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.10–0.80)

0≤0.351.4

Missense OE?0.65 (0.52–0.81)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 2 / 7.9Missense obs/exp: 56 / 86.7Syn Z: 0.92

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS31

Likely Benign14

Benign12

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	1	0	0	1
VUS	30	1	0	31
Likely Benign	2	9	3	14
Benign	2	10	0	12
Total	36	20	3	59

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

25 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap TSEN15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →