TRMT5

tRNA methyltransferase 5, the group of 7BS DNA/RNA methyltransferases

Basic information

Region (hg38): 14:60971440-60981170

Previous symbols: [ "KIAA1393" ]

Links

ENSG00000126814 ∙ NCBI:57570 ∙ OMIM:611023 ∙ HGNC:23141 ∙ Uniprot:Q32P41 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 26 (Supportive), mode of inheritance: AR
• combined oxidative phosphorylation defect type 26 (Moderate), mode of inheritance: AR
• combined oxidative phosphorylation defect type 26 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay	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	Biochemical; Neurologic	26189817

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRMT5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRMT5 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	52	2	56
missense			93	10	2	105
nonsense			3			3
start loss						0
frameshift		1	7			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			6	5	4	15
non coding			1	14	5	20
Total	0	1	107	76	9

Variants in TRMT5

This is a list of pathogenic ClinVar variants found in the TRMT5 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-60975112-A-C			Uncertain significance (Sep 01, 2023)
14-60975114-T-C			Uncertain significance (Mar 11, 2022)
14-60975127-T-C			Likely benign (Dec 02, 2021)
14-60975139-G-A			Likely benign (Oct 03, 2023)
14-60975157-C-T			Likely benign (Aug 03, 2023)
14-60975158-G-A		Combined oxidative phosphorylation defect type 26 • TRMT5-related disorder	Likely benign (Jan 02, 2024)
14-60975177-G-A			Uncertain significance (Jan 17, 2022)
14-60975178-T-C			Benign (Jan 26, 2024)
14-60975180-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 15, 2024)
14-60975182-T-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
14-60975183-C-A			Uncertain significance (Jul 15, 2022)
14-60975189-G-A			Likely benign (Jan 22, 2024)
14-60975197-G-C			Uncertain significance (Mar 12, 2022)
14-60975471-T-C			Uncertain significance (Mar 13, 2022)
14-60975477-G-C			Uncertain significance (Mar 10, 2022)
14-60975478-G-C		Inborn genetic diseases	Uncertain significance (May 14, 2024)
14-60975498-T-G			Uncertain significance (Aug 19, 2022)
14-60975500-G-C		TRMT5-related disorder	Likely benign (Mar 21, 2022)
14-60975502-G-A			Uncertain significance (Jul 17, 2022)
14-60975507-G-A			Uncertain significance (Jun 21, 2022)
14-60975524-C-G			Likely benign (Mar 04, 2022)
14-60975550-G-T			Uncertain significance (Aug 15, 2022)
14-60975554-C-T			Likely benign (Dec 02, 2021)
14-60975584-T-C			Likely benign (Apr 24, 2023)
14-60975586-C-T			Uncertain significance (Dec 07, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRMT5	protein_coding	protein_coding	ENST00000261249	5	9908

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0498	0.949	125481	0	265	125746	0.00105

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.102	252	257	0.982	0.0000129	3355
Missense in Polyphen		51	58.161	0.87688		736
Synonymous	-0.800	104	94.1	1.10	0.00000468	975
Loss of Function	2.92	6	20.1	0.298	0.00000125	244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000937	0.000937
Ashkenazi Jewish	0.00337	0.00338
East Asian	0.000272	0.000272
Finnish	0.000231	0.000231
European (Non-Finnish)	0.00147	0.00147
Middle Eastern	0.000272	0.000272
South Asian	0.000686	0.000653
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in mitochondrial tRNA methylation (PubMed:26189817). Specifically methylates the N1 position of guanosine-37 in various tRNAs. Methylation is not dependent on the nature of the nucleoside 5' of the target nucleoside. This is the first step in the biosynthesis of wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and required for accurate decoding. {ECO:0000269|PubMed:26189817}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 26 (COXPD26) [MIM:616539]: A mitochondrial disorder characterized by lactic acidosis, multiple mitochondrial respiratory-chain-complex deficiencies in skeletal muscle, and additional variable features including hypertrophic cardiomyopathy, exercise intolerance, and failure to thrive. {ECO:0000269|PubMed:26189817}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Synthesis of wybutosine at G37 of tRNA(Phe);tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.0876

Intolerance Scores

• loftool: 0.792
• rvis_EVS: 0.18
• rvis_percentile_EVS: 66.07

Haploinsufficiency Scores

• pHI: 0.164
• hipred: Y
• hipred_score: 0.502
• ghis: 0.573

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.260

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trmt5

Gene ontology

• Biological process: tRNA N1-guanine methylation;tRNA methylation;mitochondrial tRNA methylation
• Cellular component: nucleus;cytoplasm;mitochondrial matrix
• Molecular function: tRNA methyltransferase activity;tRNA (guanine-N1-)-methyltransferase activity;tRNA (guanine(37)-N(1))-methyltransferase activity