SCN10A
Basic information
Region (hg38): 3:38696801-38816286
Links
Phenotypes
GenCC
Source:
- Brugada syndrome (Limited), mode of inheritance: Unknown
- episodic pain syndrome, familial, 2 (Limited), mode of inheritance: AD
- episodic pain syndrome, familial, 2 (No Known Disease Relationship), mode of inheritance: AD
- sodium channelopathy-related small fiber neuropathy (Supportive), mode of inheritance: AD
- episodic pain syndrome, familial, 2 (Limited), mode of inheritance: AD
- Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Episodic pain syndrome, familial, 2 | AD | 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 | Neurologic | 23115331 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCN10A 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 | 12 | 439 | 11 | 462 | ||
missense | 885 | 77 | 968 | |||
nonsense | 34 | 34 | ||||
start loss | 1 | |||||
frameshift | 47 | 47 | ||||
inframe indel | 11 | 13 | ||||
splice donor/acceptor (+/-2bp) | 19 | 19 | ||||
splice region | 30 | 36 | 1 | 67 | ||
non coding | 137 | 53 | 194 | |||
Total | 0 | 1 | 1013 | 654 | 70 |
Variants in SCN10A
This is a list of pathogenic ClinVar variants found in the SCN10A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
3-38697226-G-A | Benign (Jun 19, 2018) | |||
3-38697302-C-T | Likely benign (Jul 27, 2018) | |||
3-38697354-G-T | Brugada syndrome • Cardiovascular phenotype | Uncertain significance (Apr 27, 2024) | ||
3-38697357-C-T | Brugada syndrome • Cardiovascular phenotype | Uncertain significance (Feb 16, 2024) | ||
3-38697362-G-A | Brugada syndrome • Cardiovascular phenotype | Uncertain significance (Oct 12, 2021) | ||
3-38697362-G-C | Cardiovascular phenotype | Uncertain significance (May 06, 2023) | ||
3-38697363-C-A | Cardiovascular phenotype | Uncertain significance (Feb 06, 2024) | ||
3-38697364-A-G | Brugada syndrome | Likely benign (May 27, 2022) | ||
3-38697367-C-A | Brugada syndrome | Likely benign (Mar 17, 2023) | ||
3-38697369-G-A | Brugada syndrome | Likely benign (Dec 31, 2023) | ||
3-38697374-A-G | Cardiovascular phenotype | Likely benign (Jun 18, 2024) | ||
3-38697374-A-T | Cardiovascular phenotype | Likely benign (Jan 05, 2022) | ||
3-38697382-G-A | Brugada syndrome | Likely benign (Nov 01, 2022) | ||
3-38697386-T-C | not specified • Brugada syndrome • Cardiovascular phenotype | Benign/Likely benign (Dec 08, 2023) | ||
3-38697393-C-A | Brugada syndrome | Uncertain significance (Jul 23, 2020) | ||
3-38697400-T-C | Brugada syndrome • Cardiovascular phenotype | Conflicting classifications of pathogenicity (Mar 13, 2023) | ||
3-38697403-T-G | Brugada syndrome | Likely benign (May 17, 2021) | ||
3-38697410-G-C | Cardiovascular phenotype | Uncertain significance (Dec 04, 2023) | ||
3-38697411-A-G | Cardiovascular phenotype | Uncertain significance (Dec 18, 2022) | ||
3-38697416-C-T | Cardiovascular phenotype • Brugada syndrome | Uncertain significance (Feb 06, 2022) | ||
3-38697420-T-A | Cardiovascular phenotype | Likely benign (May 21, 2024) | ||
3-38697428-C-CT | Brugada syndrome | Uncertain significance (Jun 21, 2021) | ||
3-38697431-T-A | Brugada syndrome • Cardiovascular phenotype | Likely benign (Aug 22, 2022) | ||
3-38697432-C-T | Brugada syndrome | Uncertain significance (Mar 15, 2023) | ||
3-38697439-G-A | Brugada syndrome | Likely benign (Dec 09, 2018) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SCN10A | protein_coding | protein_coding | ENST00000449082 | 27 | 97209 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
9.95e-38 | 0.00100 | 125493 | 0 | 255 | 125748 | 0.00101 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -0.682 | 1144 | 1.08e+3 | 1.06 | 0.0000612 | 12933 |
Missense in Polyphen | 421 | 436.11 | 0.96536 | 5427 | ||
Synonymous | -1.93 | 465 | 415 | 1.12 | 0.0000239 | 3820 |
Loss of Function | 1.44 | 65 | 78.8 | 0.825 | 0.00000437 | 902 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00192 | 0.00192 |
Ashkenazi Jewish | 0.000496 | 0.000496 |
East Asian | 0.00212 | 0.00212 |
Finnish | 0.000278 | 0.000277 |
European (Non-Finnish) | 0.000989 | 0.000985 |
Middle Eastern | 0.00212 | 0.00212 |
South Asian | 0.000887 | 0.000882 |
Other | 0.00179 | 0.00179 |
dbNSFP
Source:
- Function
- FUNCTION: Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium- selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms. {ECO:0000269|PubMed:9839820}.;
- Disease
- DISEASE: Episodic pain syndrome, familial, 2 (FEPS2) [MIM:615551]: An autosomal dominant neurologic disorder characterized by adult- onset of paroxysmal pain mainly affecting the distal lower extremities. {ECO:0000269|PubMed:23115331}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Lidocaine (Local Anaesthetic) Metabolism Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Developmental Biology;Phase 0 - rapid depolarisation;Cardiac conduction;Muscle contraction;Interaction between L1 and Ankyrins;L1CAM interactions;Axon guidance
(Consensus)
Recessive Scores
- pRec
- 0.0970
Intolerance Scores
- loftool
- 0.0382
- rvis_EVS
- -1.32
- rvis_percentile_EVS
- 4.74
Haploinsufficiency Scores
- pHI
- 0.190
- hipred
- Y
- hipred_score
- 0.520
- ghis
- 0.462
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.205
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Scn10a
- 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Gene ontology
- Biological process
- regulation of heart rate;sensory perception;neuronal action potential;sensory perception of pain;regulation of ion transmembrane transport;sodium ion transmembrane transport;odontogenesis of dentin-containing tooth;regulation of cardiac muscle contraction;regulation of atrial cardiac muscle cell membrane depolarization;membrane depolarization during action potential;AV node cell action potential;bundle of His cell action potential
- Cellular component
- voltage-gated sodium channel complex;plasma membrane;axon;extracellular exosome;clathrin complex;glutamatergic synapse;integral component of presynaptic membrane
- Molecular function
- voltage-gated ion channel activity;voltage-gated sodium channel activity;ion channel binding