TRNT1

tRNA nucleotidyl transferase 1

Basic information

Region (hg38): 3:3126933-3153435

Links

ENSG00000072756 ∙ NCBI:51095 ∙ OMIM:612907 ∙ HGNC:17341 ∙ Uniprot:Q96Q11 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (Strong), mode of inheritance: AR
• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (Supportive), mode of inheritance: AR
• retinitis pigmentosa and erythrocytic microcytosis (Definitive), mode of inheritance: AR
• retinitis pigmentosa and erythrocytic microcytosis (Strong), mode of inheritance: AR
• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (Strong), mode of inheritance: AR
• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic	Medical management (with immunoglobulin therapy) has been described as beneficial; Most patients have been described as requiring regular blood transfusions for treatment of anemia, as well as iron chelation; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; BMT has been described	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Hematologic; Neurologic; Ophthalmologic; Renal	25193871; 26494905

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRNT1 gene.

• Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (52 variants)
• TRNT1-related disorder (2 variants)
• not provided (2 variants)
• Retinitis pigmentosa and erythrocytic microcytosis (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRNT1 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			4	89	3	96
missense	1	3	233	3	3	243
nonsense	11	1	1			13
start loss			1			1
frameshift	34	6	2			42
inframe indel		1	3	1		5
splice donor/acceptor (+/-2bp)	5	1	1	1		8
splice region			13	11		24
non coding	1	1	9	73	38	122
Total	52	13	254	167	44

Highest pathogenic variant AF is 0.0000788

Variants in TRNT1

This is a list of pathogenic ClinVar variants found in the TRNT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-3126942-C-A			Benign (Nov 24, 2021)
3-3126954-C-CGTGGCGGCG			Likely benign (Apr 12, 2018)
3-3126968-C-T		not specified	Likely benign (Oct 16, 2017)
3-3126971-C-T		not specified	Likely benign (Aug 17, 2016)
3-3126985-G-A		not specified	Likely benign (Dec 22, 2017)
3-3126999-G-A		not specified	Likely benign (Nov 25, 2017)
3-3127000-C-G		not specified	Likely benign (Apr 15, 2016)
3-3127007-C-G		not specified	Likely benign (Jun 21, 2017)
3-3127088-C-A			Benign (Nov 24, 2021)
3-3128725-G-C			Benign (Jun 14, 2018)
3-3128776-A-AGTT			Benign (Jul 17, 2018)
3-3128946-C-T			Likely benign (Jul 27, 2018)
3-3128947-C-G			Benign (Jul 28, 2018)
3-3128994-C-G		not specified	Likely benign (Sep 21, 2017)
3-3128995-CTGTG-C			Likely benign (Jul 19, 2018)
3-3129001-A-T			Likely benign (Apr 17, 2018)
3-3129018-G-A		not specified	Likely benign (May 31, 2017)
3-3129041-A-G		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Oct 14, 2021)
3-3129041-ATGCTGAGG-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Pathogenic (Jan 03, 2023)
3-3129044-C-T		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Likely benign (Oct 17, 2023)
3-3129052-C-T		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Apr 18, 2022)
3-3129055-G-A		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Likely benign (Nov 15, 2023)
3-3129067-C-G		Inborn genetic diseases • Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Jul 31, 2023)
3-3129067-C-T		not specified • Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Likely benign (Apr 25, 2023)
3-3129071-C-G		Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome	Uncertain significance (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRNT1	protein_coding	protein_coding	ENST00000251607	7	23964

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000159	0.971	125615	0	133	125748	0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.15	273	225	1.22	0.0000109	2865
Missense in Polyphen		81	72.514	1.117		874
Synonymous	0.244	76	78.8	0.965	0.00000390	786
Loss of Function	1.95	9	17.9	0.502	7.48e-7	255

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00100
Ashkenazi Jewish	0.00	0.00
East Asian	0.000507	0.000489
Finnish	0.000376	0.000370
European (Non-Finnish)	0.000709	0.000686
Middle Eastern	0.000507	0.000489
South Asian	0.000387	0.000359
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Adds and repairs the conserved 3'-CCA sequence necessary for the attachment of amino acids to the 3' terminus of tRNA molecules, using CTP and ATP as substrates. {ECO:0000269|PubMed:11504732}.
• Disease: DISEASE: Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) [MIM:616084]: An autosomal recessive disease characterized by severe sideroblastic anemia with onset in the neonatal period or infancy, recurrent periodic fevers without an infectious etiology, B-cell lymphopenia and hypogammaglobulinemia. Affected individuals show delayed psychomotor development with variable neurodegeneration. Additional variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy. {ECO:0000269|PubMed:25193871}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa and erythrocytic microcytosis (RPEM) [MIM:616959]: An autosomal recessive disease characterized by retinitis pigmentosa, red blood cell microcytosis and anisocytosis with mild anemia. {ECO:0000269|PubMed:26494905}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA transport - Homo sapiens (human);tRNA processing;Metabolism of RNA;tRNA processing in the mitochondrion;tRNA processing in the nucleus (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.899
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.91

Haploinsufficiency Scores

• pHI: 0.0863
• hipred: N
• hipred_score: 0.251
• ghis: 0.674

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.808

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trnt1
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype

Zebrafish Information Network

• Gene name: trnt1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: tRNA 3'-terminal CCA addition;tRNA 3'-end processing;mitochondrial tRNA 3'-end processing
• Cellular component: nucleoplasm;mitochondrion;mitochondrial matrix
• Molecular function: tRNA binding;ATP binding;5'-3' RNA polymerase activity;CTP:tRNA cytidylyltransferase activity;CTP:3'-cytidine-tRNA cytidylyltransferase activity;ATP:3'-cytidine-cytidine-tRNA adenylyltransferase activity