TRMT10A

protein-coding

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

Gene summary

This gene encodes a protein that belongs to the tRNA (Guanine-1)-methyltransferase family. A similar gene in yeast modifies several different tRNA species. Mutations in this gene are associated with microcephaly, short stature, and impaired glucose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

Previous symbols:

RG9MTD2

MANE transcript

NM_001134665.3

Inheritance

ClinVar variants

P:26U:80B:32

Top phenotype

Microcephaly, short stature, and impaired glucose metabolism 1

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr4:99,546,709-99,564,039

External References & Databases

Ensembl (ENSG00000145331)

Transcript & Mutation Effects

hg38 • Region Span ~17.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microcephaly, short stature, and impaired glucose metabolism 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0000208

Submitter: Labcorp Genetics (formerly Invitae)

microcephaly, short stature, and impaired glucose metabolism 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0000208

Submitter: G2P

primary microcephaly-mild intellectual disability-young-onset diabetes syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018320

Submitter: Orphanet

microcephaly, short stature, and impaired glucose metabolism 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0000208

Submitter: PanelApp Australia

microcephaly, short stature, and impaired glucose metabolism 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0000208

Submitter: Ambry Genetics

microcephaly, short stature, and impaired glucose metabolism 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0000208

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Microcephaly, short stature, and impaired glucose metabolism 1AR

Manifestation: Craniofacial; Endocrine; Musculoskeletal; Neurologic

Intervention: Endocrine

Rationale: Awareness of the risk of diabetes mellitus may allow prompt recognition and treatment

Refs: 24204302; 25053765

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRMT10A variants in ClinVar

8 Conditions Cataloged

not providedTotal: 113

Inborn genetic diseasesTotal: 43

Microcephaly, short stature, and impaired glucose metabolism 1Total: 23

not specifiedTotal: 13

TRMT10A-related disorderTotal: 7

Abnormality of the nervous systemTotal: 1

Syndromic Monogenic DiabetesTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001134665.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				25 clinvar		25
missense	1 clinvar		74 clinvar	7 clinvar		82
nonsense	8 clinvar	6 clinvar	2 clinvar			16
start loss						0
frameshift		6 clinvar	4 clinvar			10
splice donor/acceptor (+/-2bp)		5 clinvar				5
Total	9	17	80	32	0	138

Highest pathogenic variant AF is 0.0003117574

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001134665.3	RefSeq	NP_001128137.1	7	MANE Select
ENST00000394876.7	Ensembl	ENSP00000378342.2	7	MANE Select
NM_001134666.3	RefSeq	NP_001128138.1	7	Standard
NM_001375880.1	RefSeq	NP_001362809.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA

Biological Process

tRNA methylation

Molecular Function

tRNA binding
RNA binding
tRNA (guanine-N1-)-methyltransferase activity
tRNA (guanine(9)-N(1))-methyltransferase activity

Cellular Component

nucleus
nucleoplasm
nucleolus
cytosol
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000273962
Coding exons: 7
Length: 17324
Individuals with no LoFs: 125649
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125741
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.436	166	183	0.909	0.00000978	2254
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00044	0.00044	rare
Finnish	0.0012	0.0012	notable
European (Non-Finnish)	0.00037	0.00037	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.0909

Intolerance Scores

RVIS EVS: 0.33
RVIS percentile EVS: 73.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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