SIL1
Basic information
Region (hg38): 5:138946724-139293557
Previous symbols: [ "MSS" ]
Links
Phenotypes
GenCC
Source:
- Marinesco-Sjogren syndrome (Definitive), mode of inheritance: AR
- Marinesco-Sjogren syndrome (Strong), mode of inheritance: AR
- Marinesco-Sjogren syndrome (Supportive), mode of inheritance: AR
- Marinesco-Sjogren syndrome (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Marinesco-Sjogren syndrome | 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 | Endocrine; Musculoskeletal; Neurologic; Ophthalmologic | 13053231; 830450; 3683758; 10665502; 14512967; 16282978; 16282977; 17309654; 18285827; 20301371; 20111056; 22219183; 23062754 |
ClinVar
This is a list of variants' phenotypes submitted to
- Marinesco-Sjögren syndrome (13 variants)
- not provided (6 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIL1 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 | 63 | 70 | ||||
missense | 138 | 147 | ||||
nonsense | 6 | |||||
start loss | 2 | |||||
frameshift | 10 | 12 | ||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 7 | |||||
splice region | 4 | 5 | 2 | 11 | ||
non coding | 13 | 37 | 14 | 65 | ||
Total | 17 | 8 | 160 | 107 | 18 |
Highest pathogenic variant AF is 0.0000920
Variants in SIL1
This is a list of pathogenic ClinVar variants found in the SIL1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
5-138946768-A-G | Marinesco-Sjögren syndrome | Uncertain significance (Jan 12, 2018) | ||
5-138946852-G-C | Marinesco-Sjögren syndrome | Uncertain significance (Jan 12, 2018) | ||
5-138947012-G-A | Marinesco-Sjögren syndrome | Uncertain significance (Jan 12, 2018) | ||
5-138947037-C-G | Marinesco-Sjögren syndrome | Uncertain significance (Jan 13, 2018) | ||
5-138947048-AG-A | Marinesco-Sjögren syndrome | Uncertain significance (Jun 14, 2016) | ||
5-138947087-G-A | Marinesco-Sjögren syndrome | Uncertain significance (Jun 14, 2016) | ||
5-138947123-C-G | Marinesco-Sjögren syndrome | Likely benign (Aug 01, 2022) | ||
5-138947133-A-G | Marinesco-Sjögren syndrome | Pathogenic (Aug 01, 2008) | ||
5-138947135-C-T | Marinesco-Sjögren syndrome | Likely benign (Aug 27, 2023) | ||
5-138947139-C-T | Marinesco-Sjögren syndrome | Uncertain significance (Nov 06, 2019) | ||
5-138947145-A-G | Inborn genetic diseases | Uncertain significance (Mar 17, 2023) | ||
5-138947152-C-T | not specified • SIL1-related disorder • Marinesco-Sjögren syndrome | Benign/Likely benign (Jan 22, 2024) | ||
5-138947156-C-T | Marinesco-Sjögren syndrome | Likely benign (Sep 19, 2023) | ||
5-138947161-C-T | Marinesco-Sjögren syndrome | Uncertain significance (Apr 26, 2023) | ||
5-138947172-C-A | Marinesco-Sjögren syndrome | Uncertain significance (Jul 17, 2022) | ||
5-138947173-C-A | Marinesco-Sjögren syndrome | Uncertain significance (Jun 20, 2023) | ||
5-138947177-G-A | Marinesco-Sjögren syndrome • SIL1-related disorder | Likely benign (Nov 27, 2021) | ||
5-138947182-C-A | Marinesco-Sjögren syndrome | Pathogenic (Jun 17, 2019) | ||
5-138947182-C-T | Marinesco-Sjögren syndrome | Uncertain significance (Jan 17, 2024) | ||
5-138947183-A-G | SIL1-related disorder | Likely benign (Jul 27, 2021) | ||
5-138947186-A-G | Marinesco-Sjögren syndrome | Likely benign (Apr 13, 2023) | ||
5-138947187-T-C | Marinesco-Sjögren syndrome | Uncertain significance (Aug 09, 2022) | ||
5-138947191-G-A | Marinesco-Sjögren syndrome | Pathogenic (Jul 22, 2021) | ||
5-138947217-T-A | Marinesco-Sjögren syndrome • Inborn genetic diseases | Uncertain significance (May 25, 2022) | ||
5-138947221-C-G | Marinesco-Sjögren syndrome | Uncertain significance (Jun 08, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SIL1 | protein_coding | protein_coding | ENST00000394817 | 9 | 346838 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.0123 | 0.986 | 125680 | 0 | 68 | 125748 | 0.000270 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.471 | 234 | 255 | 0.917 | 0.0000158 | 2986 |
Missense in Polyphen | 89 | 95.05 | 0.93635 | 1120 | ||
Synonymous | -0.636 | 127 | 118 | 1.07 | 0.00000793 | 934 |
Loss of Function | 2.79 | 7 | 20.7 | 0.338 | 9.89e-7 | 240 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000116 | 0.000116 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.0000552 | 0.0000544 |
Finnish | 0.000835 | 0.000832 |
European (Non-Finnish) | 0.000328 | 0.000316 |
Middle Eastern | 0.0000552 | 0.0000544 |
South Asian | 0.000132 | 0.000131 |
Other | 0.000862 | 0.000815 |
dbNSFP
Source:
- Function
- FUNCTION: Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5. {ECO:0000269|PubMed:12356756}.;
- Disease
- DISEASE: Marinesco-Sjoegren syndrome (MSS) [MIM:248800]: Autosomal recessive multisystem disorder which is characterized by cerebellar ataxia due to cerebellar atrophy, with Purkinje and granule cell loss and myopathy featuring marked muscle replacement with fat and connective tissue. Other cardinal features include bilateral cataracts, hypergonadotrophic hypogonadism and mild to severe mental retardation. Skeletal abnormalities, short stature, dysarthria, strabismus and nystagmus are also frequent findings. Mutational inactivation of this protein may result in ER stress- induced cell death signaling or malfunctioning chaperone machineries that mishandle client proteins which are critical for the organs targeted in MSS. {ECO:0000269|PubMed:16282977, ECO:0000269|PubMed:16282978}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Protein processing in endoplasmic reticulum - Homo sapiens (human)
(Consensus)
Recessive Scores
- pRec
- 0.503
Intolerance Scores
- loftool
- 0.747
- rvis_EVS
- 0.42
- rvis_percentile_EVS
- 77.23
Haploinsufficiency Scores
- pHI
- 0.0687
- hipred
- Y
- hipred_score
- 0.504
- ghis
- 0.428
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.344
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sil1
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- sil1
- Affected structure
- Purkinje cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- protein folding;intracellular protein transport;regulation of catalytic activity
- Cellular component
- extracellular space;cytoplasm;endoplasmic reticulum;endoplasmic reticulum lumen
- Molecular function
- adenyl-nucleotide exchange factor activity;protein binding;unfolded protein binding