TRMT10A

tRNA methyltransferase 10A, the group of SPOUT methyltransferase domain containing

Basic information

Region (hg38): 4:99546709-99564039

Previous symbols: [ "RG9MTD2" ]

Links

ENSG00000145331 ∙ NCBI:93587 ∙ OMIM:616013 ∙ HGNC:28403 ∙ Uniprot:Q8TBZ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 68 (Definitive), mode of inheritance: AR
• microcephaly, short stature, and impaired glucose metabolism 1 (Strong), mode of inheritance: AR
• microcephaly, short stature, and impaired glucose metabolism 1 (Strong), mode of inheritance: AR
• primary microcephaly-mild intellectual disability-young-onset diabetes syndrome (Supportive), mode of inheritance: AR
• microcephaly, short stature, and impaired glucose metabolism 1 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, short stature, and impaired glucose metabolism 1	AR	Endocrine	Awareness of the risk of diabetes mellitus may allow prompt recognition and treatment	Craniofacial; Endocrine; Musculoskeletal; Neurologic	24204302; 25053765

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRMT10A gene.

• Microcephaly, short stature, and impaired glucose metabolism 1 (3 variants)
• not provided (3 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRMT10A 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			1	20		21
missense	1		57	2		60
nonsense	4	4	2			10
start loss						0
frameshift	1	1	2			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region			3	3		6
non coding				10	3	13
Total	6	8	63	32	3

Highest pathogenic variant AF is 0.000151

Variants in TRMT10A

This is a list of pathogenic ClinVar variants found in the TRMT10A region.

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

Position	Type	Phenotype	Significance	ClinVar
4-99549092-T-C			Uncertain significance (Aug 10, 2023)
4-99549130-C-T			Likely benign (Apr 23, 2021)
4-99549136-C-T			Likely benign (Sep 19, 2022)
4-99549153-G-T		not specified • TRMT10A-related disorder	Conflicting classifications of pathogenicity (Jan 26, 2024)
4-99549162-G-C			Uncertain significance (Mar 18, 2022)
4-99549174-T-C		not specified • Inborn genetic diseases	Uncertain significance (Apr 18, 2024)
4-99549194-T-TCACTGTC			Uncertain significance (Apr 06, 2022)
4-99549202-C-T			Likely benign (Feb 01, 2023)
4-99549209-C-T			Uncertain significance (Oct 24, 2022)
4-99549210-C-G		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
4-99549220-C-T			Likely benign (Dec 18, 2018)
4-99549233-T-C			Uncertain significance (Aug 09, 2022)
4-99549239-TGAG-T		not specified	Uncertain significance (Jan 08, 2016)
4-99549240-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
4-99549254-C-T		not specified	Uncertain significance (May 03, 2022)
4-99549271-A-T		not specified	Likely benign (Jun 08, 2016)
4-99549284-C-T			Uncertain significance (Aug 10, 2023)
4-99549285-G-T			Uncertain significance (Dec 27, 2020)
4-99549287-TG-T			Uncertain significance (Jul 07, 2022)
4-99549314-T-C			Uncertain significance (Jul 23, 2022)
4-99549323-C-T		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
4-99549360-C-T			Likely benign (Aug 09, 2022)
4-99549376-C-T			Benign (Jan 22, 2024)
4-99550866-T-G			Likely benign (Mar 01, 2022)
4-99550909-G-A			Uncertain significance (Aug 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRMT10A	protein_coding	protein_coding	ENST00000273962	7	17324

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.89e-10	0.331	125649	0	92	125741	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.436	166	183	0.909	0.00000978	2254
Missense in Polyphen		55	57.955	0.94901		661
Synonymous	1.24	49	61.4	0.798	0.00000314	585
Loss of Function	0.905	17	21.5	0.789	0.00000149	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000326	0.000326
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000442	0.000435
Finnish	0.00123	0.00120
European (Non-Finnish)	0.000372	0.000369
Middle Eastern	0.000442	0.000435
South Asian	0.000131	0.000131
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: S-adenosyl-L-methionine-dependent guanine N(1)- methyltransferase that catalyzes the formation of N(1)- methylguanine at position 9 (m1G9) in tRNAs (PubMed:23042678, PubMed:25053765). Probably not able to catalyze formation of N(1)- methyladenine at position 9 (m1A9) in tRNAs (PubMed:23042678). {ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25053765}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.0909

Intolerance Scores

• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.27

Haploinsufficiency Scores

• pHI: 0.143
• hipred: N
• hipred_score: 0.169
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trmt10a
• Phenotype: growth/size/body region phenotype; skeleton phenotype; homeostasis/metabolism phenotype; vision/eye phenotype

Gene ontology

• Biological process: tRNA methylation
• Cellular component: nucleus;nucleoplasm;nucleolus;cytosol;actin cytoskeleton;extracellular exosome
• Molecular function: tRNA binding;RNA binding;tRNA (guanine-N1-)-methyltransferase activity;tRNA (guanine(9)-N(1))-methyltransferase activity