NSUN3

NOP2/Sun RNA methyltransferase 3, the group of NOP2/Sun RNA methyltransferase family

Basic information

Region (hg38): 3:94062980-94131832

Links

ENSG00000178694 ∙ NCBI:63899 ∙ OMIM:617491 ∙ HGNC:26208 ∙ Uniprot:Q9H649 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 48 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 48	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	Biochemical; Neurologic	27356879; 32488845

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NSUN3 gene.

• not_provided (81 variants)
• Inborn_genetic_diseases (44 variants)
• Combined_oxidative_phosphorylation_deficiency_48 (7 variants)
• not_specified (2 variants)
• NSUN3-related_disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSUN3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022072.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				22	2	24
missense	2		68	4	1	75
nonsense	1	1	3			5
start loss			1			1
frameshift		1				1
splice donor/acceptor (+/-2bp)	2		3			5
Total	5	2	75	26	3

Highest pathogenic variant AF is 0.00008801835

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSUN3	protein_coding	protein_coding	ENST00000314622	6	65630

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.04e-9	0.301	125702	0	45	125747	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.306	164	175	0.935	0.00000842	2200
Missense in Polyphen		64	66.343	0.96468		845
Synonymous	0.920	58	67.6	0.858	0.00000347	657
Loss of Function	0.668	14	17.0	0.825	9.51e-7	202

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000928	0.000926
Ashkenazi Jewish	0.00	0.00
East Asian	0.000327	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000327	0.000326
South Asian	0.0000982	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial tRNA methyltransferase that mediates methylation of cytosine to 5-methylcytosine (m5C) at position 34 of mt-tRNA(Met) (PubMed:27497299, PubMed:27214402, PubMed:27356879). mt-tRNA(Met) methylation at cytosine(34) takes place at the wobble position of the anticodon and initiates the formation of 5-formylcytosine (f(5)c) at this position (PubMed:27497299, PubMed:27214402, PubMed:27356879). mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation (PubMed:27497299, PubMed:27356879). {ECO:0000269|PubMed:27214402, ECO:0000269|PubMed:27356879, ECO:0000269|PubMed:27497299}.
• Disease: DISEASE: Note=Mitochondrial complex deficiency (PubMed:27356879). A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected (PubMed:27356879). Clinical features include combined developmental disability, microcephaly, failure to thrive, recurrent increased lactate levels in plasma, muscular weakness, proximal accentuated, external ophthalmoplegia and convergence nystagmus (PubMed:27356879). Defects are probably caused by deficient methylation and formylation of mt-tRNA(Met) wobble cytosine (PubMed:27356879). The disease may be caused by mutations affecting the gene represented in this entry. {ECO:0000269|PubMed:27356879}.

Recessive Scores

• pRec: 0.0960

Intolerance Scores

• loftool: 0.830
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.11

Haploinsufficiency Scores

• pHI: 0.866
• hipred: N
• hipred_score: 0.251
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.892

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nsun3

Gene ontology

• Biological process: tRNA wobble base cytosine methylation;rRNA methylation;regulation of mitochondrial translation
• Cellular component: mitochondrion;mitochondrial matrix;mitochondrial large ribosomal subunit
• Molecular function: tRNA binding;methyltransferase activity;tRNA (cytosine-5-)-methyltransferase activity