ACSF3
Basic information
Region (hg38): 16:89088375-89164121
Links
Phenotypes
GenCC
Source:
- combined malonic and methylmalonic acidemia (Strong), mode of inheritance: AR
- combined malonic and methylmalonic acidemia (Supportive), mode of inheritance: AD
- combined malonic and methylmalonic acidemia (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Combined malonic and methylmalonic aciduria | AR | Biochemical | Although the optimal treatment (as well as the requirement thereof) is currently unclear, additional monitoring may be warranted to determine whether medical management would be beneficial | Biochemical; Neurologic | 9700595; 21785126; 21841779; 30740739 |
ClinVar
This is a list of variants' phenotypes submitted to
- Combined_malonic_and_methylmalonic_acidemia (851 variants)
- Inborn_genetic_diseases (109 variants)
- not_provided (87 variants)
- Methylmalonic_acidemia (66 variants)
- not_specified (59 variants)
- ACSF3-related_disorder (31 variants)
- Global_developmental_delay (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACSF3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001243279.3. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
---|---|---|---|---|---|---|
synonymous | 15 | 339 | 362 | |||
missense | 18 | 242 | 18 | 279 | ||
nonsense | 16 | 46 | 62 | |||
start loss | 1 | 1 | ||||
frameshift | 23 | 55 | 79 | |||
splice donor/acceptor (+/-2bp) | 31 | 33 | ||||
Total | 42 | 153 | 258 | 357 | 6 |
Highest pathogenic variant AF is 0.0045165
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
ACSF3 | protein_coding | protein_coding | ENST00000317447 | 9 | 67472 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
2.32e-26 | 0.00000743 | 125624 | 1 | 123 | 125748 | 0.000493 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -1.30 | 426 | 357 | 1.19 | 0.0000238 | 3652 |
Missense in Polyphen | 153 | 128.82 | 1.1877 | 1337 | ||
Synonymous | -2.81 | 207 | 161 | 1.28 | 0.0000122 | 1207 |
Loss of Function | -1.62 | 34 | 25.2 | 1.35 | 0.00000134 | 264 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000844 | 0.000843 |
Ashkenazi Jewish | 0.0000993 | 0.0000992 |
East Asian | 0.00127 | 0.00125 |
Finnish | 0.0000928 | 0.0000924 |
European (Non-Finnish) | 0.000385 | 0.000378 |
Middle Eastern | 0.00127 | 0.00125 |
South Asian | 0.000915 | 0.000882 |
Other | 0.000653 | 0.000652 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate, but not acetate, into their respective CoA thioester. May have some preference toward very-long-chain substrates. {ECO:0000269|PubMed:17762044, ECO:0000269|PubMed:21841779}.;
- Disease
- DISEASE: Combined malonic and methylmalonic aciduria (CMAMMA) [MIM:614265]: A metabolic disease characterized by malonic and methylmalonic aciduria, with urinary excretion of much larger amounts of methylmalonic acid than malonic acid, in the presence of normal malonyl-CoA decarboxylase activity. Clinical features include coma, ketoacidosis, hypoglycemia, failure to thrive, microcephaly, dystonia, axial hypotonia and/or developmental delay, and neurologic manifestations including seizures, psychiatric disease and/or cognitive decline. {ECO:0000269|PubMed:21841779}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Valine, leucine and isoleucine degradation - Homo sapiens (human);Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Fatty acid metabolism;Synthesis of very long-chain fatty acyl-CoAs
(Consensus)
Intolerance Scores
- loftool
- 0.925
- rvis_EVS
- -0.88
- rvis_percentile_EVS
- 10.54
Haploinsufficiency Scores
- pHI
- 0.105
- hipred
- N
- hipred_score
- 0.213
- ghis
- 0.535
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.300
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Acsf3
- Phenotype
Gene ontology
- Biological process
- fatty acid metabolic process;fatty acid biosynthetic process;long-chain fatty-acyl-CoA biosynthetic process;malonate catabolic process
- Cellular component
- mitochondrion;mitochondrial matrix
- Molecular function
- ATP binding;acid-thiol ligase activity;very long-chain fatty acid-CoA ligase activity;malonyl-CoA synthetase activity