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c.631+12C>T

SpliceS3BenignCytoplasmic · predicted
Splice variant · splice site near at position 211 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

S3 — Minimal predicted splicing impact (SpliceAI ΔS 0.01)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 211 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted.

Variant Assessment

Variant type
Splice
Schema
S3
Minimal predicted splicing impact (SpliceAI ΔS 0.01)
Domain
N-terminal cytoplasmic (intrinsically disordered)
Status
—

Therapeutic Implication · S3

SpliceAI predicts little splicing disruption at this donor (5') site (max ΔS 0.01 < 0.2; acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.01, donor-loss 0.00). 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.

Clinical Evidence

ClinVar classificationBenign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsWolfram syndrome 1
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.631+12C>T
ClinVar variantNM_006005.3(WFS1):c.631+12C>T
ClinVar accessionVCV000227153
Last evaluated2025/12/23 00:00

Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).

Classified for2★ documented assertion

ClinVar classifies this variant as Benign for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). Classic Wolfram syndrome is recessive: a single copy does not produce it, and this classification says nothing about a carrier's own risk.

  • Wolfram syndrome (classic)autosomal recessive · OMIM 222300submitted as: Wolfram syndrome 1
  • 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.

Population frequency
Global (all ancestries)
Absent from gnomAD v4
Homozygotes
Not available

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.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the c.631+12C>T card below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals matched to this S3 splice variant and its domain context.

Download c.631+12C>T PDF card ↓or markdown ↓

Full Variant Card

c.631+12C_T — WFS1 Molecular Atlas Card

Variant type: Splice site Boundary: donor (5' splice site) · intronic offset +12 Nearest protein position: ~211 (N-terminal cytoplasmic (intrinsically disordered))

Schema category: S3 — Minimal predicted splicing impact (SpliceAI ΔS 0.01)

SpliceAI predicts little splicing disruption at this donor (5') site (max ΔS 0.01 < 0.2; acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.01, donor-loss 0.00). 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: donor (5' splice site), extended splice region
  • SpliceAI delta scores (GRCh38 chr4:6291379 C>T):
    • acceptor gain 0.00 · acceptor loss 0.00
    • donor gain 0.01 · donor loss 0.00
  • Predicted outcome: Minimal predicted splicing impact (SpliceAI ΔS 0.01)

Clinical evidence

Inheritance and scope

Benign — for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)

ClinVar classifies this variant as Benign for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). Classic Wolfram syndrome is recessive: a single copy does not produce it, and this classification says nothing about a carrier's own risk.

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
  • Associated conditions: Wolfram syndrome 1
  • cDNA change: c.631+12C>T
  • ClinVar accession: VCV000227153
  • Last evaluated: 2025/12/23 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (splice pipeline) on 2026-06-08T07:51:05.645514Z. Schema: reference/card_schema_extension.md (S1–S3). WFS1: UniProt O76024, AlphaFold v6.