TRMT1

tRNA methyltransferase 1, the group of 7BS DNA/RNA methyltransferases

Basic information

Region (hg38): 19:13104902-13117567

Links

ENSG00000104907 ∙ NCBI:55621 ∙ OMIM:611669 ∙ HGNC:25980 ∙ Uniprot:Q9NXH9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual developmental disorder, autosomal recessive 68 (Moderate), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 68 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 68	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	Craniofacial; Musculoskeletal; Neurologic	21937992; 26308914; 30289604

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRMT1 gene.

• Intellectual developmental disorder, autosomal recessive 68 (6 variants)
• not provided (2 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 TRMT1 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	16	2	19
missense		2	64	7		73
nonsense	3	3	2			8
start loss			1			1
frameshift	6	5				11
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1				1
splice region	1	1	1	4		7
non coding			2		1	3
Total	9	11	72	23	3

Highest pathogenic variant AF is 0.000132

Variants in TRMT1

This is a list of pathogenic ClinVar variants found in the TRMT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-13104952-C-A		Inborn genetic diseases	Uncertain significance (Sep 22, 2022)
19-13104954-G-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
19-13104971-A-AG			Pathogenic (Jul 26, 2022)
19-13104973-G-C		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
19-13104975-G-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
19-13105012-C-T			Uncertain significance (Dec 16, 2022)
19-13105032-G-A		Inborn genetic diseases	Likely benign (Dec 03, 2021)
19-13105039-G-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
19-13105048-A-G		Inborn genetic diseases	Uncertain significance (Oct 01, 2024)
19-13105068-C-T			Uncertain significance (Dec 14, 2022)
19-13105072-G-A			Uncertain significance (Sep 13, 2022)
19-13105088-G-A		Intellectual developmental disorder, autosomal recessive 68	Uncertain significance (Jul 25, 2024)
19-13105267-C-T		Intellectual developmental disorder, autosomal recessive 68	Uncertain significance (Mar 19, 2020)
19-13105282-G-C		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
19-13105301-C-T			Likely benign (Nov 01, 2024)
19-13105311-G-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2020)
19-13105311-G-C		Inborn genetic diseases	Uncertain significance (Nov 10, 2024)
19-13105316-G-C			Uncertain significance (Dec 16, 2022)
19-13105322-T-C		Inborn genetic diseases	Likely benign (Mar 28, 2022)
19-13105328-G-A		Inborn genetic diseases	Uncertain significance (Nov 15, 2022)
19-13105361-C-T		Inborn genetic diseases	Uncertain significance (Feb 17, 2022)
19-13105364-C-G		Inborn genetic diseases	Uncertain significance (Jun 28, 2024)
19-13105541-C-T		Inborn genetic diseases	Uncertain significance (Jul 16, 2021)
19-13105551-C-A		Intellectual developmental disorder, autosomal recessive 68	Pathogenic (Jan 12, 2024)
19-13105560-G-A		Intellectual developmental disorder, autosomal recessive 68	Pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRMT1	protein_coding	protein_coding	ENST00000592062	16	12666

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.89e-12	0.821	125655	0	92	125747	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.561	406	439	0.925	0.0000290	4224
Missense in Polyphen		71	94.709	0.74966		913
Synonymous	-0.320	185	180	1.03	0.0000121	1372
Loss of Function	1.82	24	35.7	0.672	0.00000204	359

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000628	0.000610
Ashkenazi Jewish	0.00	0.00
East Asian	0.000707	0.000707
Finnish	0.0000957	0.0000924
European (Non-Finnish)	0.000355	0.000352
Middle Eastern	0.000707	0.000707
South Asian	0.000623	0.000621
Other	0.000848	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl-L-methionine as donor of the methyl groups.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.0725
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.53

Haploinsufficiency Scores

• pHI: 0.204
• hipred: N
• hipred_score: 0.428
• ghis: 0.610

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.951

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trmt1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: tRNA N2-guanine methylation;tRNA modification
• Cellular component: nucleus;nucleoplasm
• Molecular function: tRNA binding;RNA binding;tRNA (guanine-N2-)-methyltransferase activity;protein binding;metal ion binding