c.316-120T>C
SpliceS3BenignCytoplasmic · predictedS3 — Minimal predicted splicing impact (SpliceAI ΔS 0.01)
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 106 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted.
Variant Assessment
Therapeutic Implication · S3
Clinical Evidence
Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).
ClinVar classifies this variant as Benign, but does not state what it is classified for. ClinVar records no condition for this variant. A classification without a phenotype and an inheritance mode cannot be read as a statement about Wolfram syndrome risk or severity.
- Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient.
- Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
Review status: 2★ multiple submitters, no conflicts. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.
No population breakdown — the variant is absent from gnomAD v4, so no ancestry group has an observed frequency.
No homozygotes — the variant is absent from gnomAD v4 altogether.
Source: gnomAD r4, retrieved 2026-08-21. Values are allele frequencies. The carrier estimate is derived from the allele frequency (Hardy-Weinberg, ~2·AF) and is an approximation, not a published figure — where a published carrier frequency exists it outranks this column and is cited on the card.
Feed this card to Wolfram Intelligence
Download the c.316-120T>C card below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals matched to this S3 splice variant and its domain context.
Full Variant Card
c.316-120T_C — WFS1 Molecular Atlas Card
Variant type: Splice site Boundary: acceptor (3' splice site) · intronic offset -120 Nearest protein position: ~106 (N-terminal cytoplasmic (intrinsically disordered))
Schema category: S3 — Minimal predicted splicing impact (SpliceAI ΔS 0.01)
SpliceAI predicts little splicing disruption at this acceptor (3') site (max ΔS 0.01 < 0.2; acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.00, donor-loss 0.01). The variant may be tolerated or act through a weak/again-tissue-specific mechanism; wet-lab RNA validation is the arbiter before any therapeutic call.
Splice prediction
- Affected site: acceptor (3' splice site), extended splice region
- SpliceAI delta scores (GRCh38 chr4:6288867 T>C):
- acceptor gain 0.00 · acceptor loss 0.00
- donor gain 0.00 · donor loss 0.01
- Predicted outcome: Minimal predicted splicing impact (SpliceAI ΔS 0.01)
Clinical evidence
Inheritance and scope
Benign — phenotype scope not stated in ClinVar
ClinVar classifies this variant as Benign, but does not state what it is classified for. ClinVar records no condition for this variant. A classification without a phenotype and an inheritance mode cannot be read as a statement about Wolfram syndrome risk or severity.
Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient. Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
- Classification: Benign
- Review status: criteria provided, multiple submitters, no conflicts
- cDNA change: c.316-120T>C
- ClinVar accession: VCV001292284
- Last evaluated: 2018/06/23 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (splice pipeline) on 2026-06-08T07:50:06.392788Z.
Schema: reference/card_schema_extension.md (S1–S3). WFS1: UniProt O76024, AlphaFold v6.