NSUN3
Basic information
Region (hg38): 3:94062980-94131832
Links
Phenotypes
GenCC
Source:
- combined oxidative phosphorylation deficiency 48 (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- Inborn genetic diseases (1 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.
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 | 15 | 17 | ||||
| missense | 52 | 56 | ||||
| nonsense | 3 | |||||
| start loss | 1 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| splice region | 2 | 4 | 6 | |||
| non coding | 6 | |||||
| Total | 1 | 1 | 58 | 23 | 4 |
Highest pathogenic variant AF is 0.0000198
Variants in NSUN3
This is a list of pathogenic ClinVar variants found in the NSUN3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| 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:
- 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
- Phenotype
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