TRMT10C

tRNA methyltransferase 10C, mitochondrial RNase P subunit, the group of SPOUT methyltransferase domain containing|Mitochondrial RNase P complex

Basic information

Region (hg38): 3:101561868-101566446

Previous symbols: [ "RG9MTD1" ]

Links

ENSG00000174173 ∙ NCBI:54931 ∙ OMIM:615423 ∙ HGNC:26022 ∙ Uniprot:Q7L0Y3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 30 (Supportive), mode of inheritance: AR
• combined oxidative phosphorylation defect type 30 (Limited), mode of inheritance: AR
• combined oxidative phosphorylation defect type 30 (Limited), mode of inheritance: Unknown
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 30	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; Cardiovascular; Neurologic	27132592

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRMT10C gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRMT10C 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				11		11
missense		1	29	4	1	35
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	1	29	15	2

Variants in TRMT10C

This is a list of pathogenic ClinVar variants found in the TRMT10C region.

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

Position	Type	Phenotype	Significance	ClinVar
3-101564809-A-G			Uncertain significance (Mar 16, 2023)
3-101564817-T-A			Uncertain significance (Mar 17, 2023)
3-101564827-C-T			Uncertain significance (Mar 16, 2022)
3-101564851-T-C		not specified	Uncertain significance (Jul 12, 2023)
3-101564860-C-T			Uncertain significance (Dec 11, 2023)
3-101564861-A-G		not specified	Uncertain significance (Dec 08, 2023)
3-101564870-G-A			Uncertain significance (Jun 23, 2022)
3-101564884-A-G		not specified	Likely benign (Nov 09, 2022)
3-101564944-A-G			Uncertain significance (Dec 15, 2022)
3-101564948-C-G			Benign (Jan 30, 2024)
3-101564950-C-G			Uncertain significance (Feb 12, 2022)
3-101564951-C-G		not specified	Uncertain significance (Jun 12, 2023)
3-101564951-C-T		not specified	Uncertain significance (Oct 22, 2021)
3-101564996-C-G			Uncertain significance (Mar 25, 2023)
3-101565005-A-C			Uncertain significance (Jun 11, 2022)
3-101565014-G-A		not specified	Uncertain significance (Feb 06, 2024)
3-101565047-A-G		not specified	Uncertain significance (Aug 02, 2023)
3-101565054-A-G			Likely benign (Nov 01, 2022)
3-101565106-C-T			Uncertain significance (May 20, 2023)
3-101565108-A-G			Likely benign (Oct 01, 2024)
3-101565195-G-A		TRMT10C-related disorder	Likely benign (Oct 01, 2024)
3-101565205-G-A		not specified	Likely benign (Mar 24, 2023)
3-101565273-G-C			Benign/Likely benign (Jan 23, 2024)
3-101565275-T-A			Likely benign (Nov 11, 2022)
3-101565285-C-T		TRMT10C-related disorder	Likely benign (Feb 05, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRMT10C	protein_coding	protein_coding	ENST00000309922	1	4585

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000971	0.813	124756	0	34	124790	0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.769	174	205	0.849	0.00000964	2685
Missense in Polyphen		41	65.029	0.63049		856
Synonymous	0.394	66	70.2	0.940	0.00000325	721
Loss of Function	1.22	8	12.7	0.631	7.36e-7	180

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000349	0.000349
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000223
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000115	0.000115
Middle Eastern	0.000223	0.000223
South Asian	0.000230	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial tRNA N(1)-methyltransferase involved in mitochondrial tRNA maturation (PubMed:18984158, PubMed:21593607, PubMed:23042678, PubMed:27132592). Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and MRPP3, which cleaves tRNA molecules in their 5'-ends (PubMed:18984158). Together with HSD17B10/MRPP2, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity (PubMed:23042678, PubMed:29040705). The MRPP1-MRPP2 subcomplex catalyzes the formation of N(1)- methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; TRMT10C/MRPP1 acting as the catalytic N(1)-methyltransferase subunit (PubMed:23042678). The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'- end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after ELAC2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme (PubMed:29040705). In addition to tRNA N(1)-methyltransferase activity, TRMT10C/MRPP1 also acts as a mRNA N(1)-methyltransferase by mediating methylation of adenosine residues at the N(1) position of MT-ND5 mRNA (PubMed:29072297). {ECO:0000269|PubMed:18984158, ECO:0000269|PubMed:21593607, ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:27132592, ECO:0000269|PubMed:29040705, ECO:0000269|PubMed:29072297}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 30 (COXPD30) [MIM:616974]: An autosomal recessive, severe mitochondrial disease characterized by lactic acidosis, hypotonia, feeding difficulties, deafness, and respiratory failure with fatal issue. Patient skeletal muscle cells show decreased activities of mitochondrial complexes I, III and IV. {ECO:0000269|PubMed:27132592}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: tRNA processing;tRNA modification in the mitochondrion;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.0631

Intolerance Scores

• rvis_EVS: 0.42
• rvis_percentile_EVS: 76.81

Haploinsufficiency Scores

• pHI: 0.0419
• hipred: N
• hipred_score: 0.123
• ghis: 0.479

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trmt10c

Gene ontology

• Biological process: mitochondrial RNA 5'-end processing;tRNA methylation;positive regulation of mitochondrial translation;mRNA methylation;mitochondrial tRNA processing;mitochondrial tRNA 5'-end processing;mitochondrial tRNA 3'-end processing
• Cellular component: nucleoplasm;mitochondrion;mitochondrial matrix;mitochondrial ribonuclease P complex;mitochondrial nucleoid
• Molecular function: tRNA binding;RNA binding;protein binding;tRNA (guanine-N1-)-methyltransferase activity;tRNA (adenine-N1-)-methyltransferase activity;tRNA (guanine(9)-N(1))-methyltransferase activity;mRNA (adenine-N1-)-methyltransferase activity