TRMT10A

Chr 4AR

tRNA methyltransferase 10A

Also known as: HEL-S-88, MSSGM, MSSGM1, RG9MTD2, TRM10

NCBI Gene: 93587 ENSG00000145331 UniProt: Q8TBZ6 OMIM: 616013

This protein is an S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of N(1)-methylguanine at position 9 in tRNAs. Biallelic mutations cause autosomal recessive microcephaly, short stature, and impaired glucose metabolism. The gene is highly tolerant to loss-of-function variation in the general population (very low pLI score).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.181 OMIM phenotype

Clinical Summary— TRMT10A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 82 VUS of 170 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.000

Z-score 0.91

OE 0.79 (0.54–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.44Z-score

OE missense 0.91 (0.80–1.03)

166 obs / 182.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.54–1.18)

0≤0.351.4

Missense OE?0.91 (0.80–1.03)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 17 / 21.5Missense obs/exp: 166 / 182.6Syn Z: 1.24

ClinVar Variant Classifications

170 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic15

VUS82

Likely Benign46

Benign3

Conflicting7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	1	1	0	10
Likely Pathogenic	15	0	0	0	15
VUS	4	73	5	0	82
Likely Benign	0	2	19	25	46
Benign	0	0	3	0	3
Conflicting	—				7
Total	27	76	28	25	163

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap TRMT10A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →