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c.460+1G>A

SpliceS2PathogenicCytoplasmic · predicted
Splice variant · splice site near at position 154 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

S2 — Predicted frameshift skip of exon 4 (145 nt)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 154 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted.

Variant Assessment

Variant type
Splice
Schema
S2
Predicted frameshift skip of exon 4 (145 nt)
Domain
N-terminal cytoplasmic (intrinsically disordered)
Status
—

Therapeutic Implication · S2

SpliceAI predicts strong donor (5') loss (ΔS 1.00) -> skipping of exon 4 (145 nt, NOT divisible by 3), which shifts the reading frame downstream. A premature stop is predicted at ~aa 115. The frameshifted/truncated product follows the frameshift schema (F1/F2 by NMD); typically too compromised for chaperone rescue — gene-therapy track. (acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.96, donor-loss 1.00.)

Clinical Evidence

ClinVar classificationPathogenic
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditions—
Population frequency (gnomAD v4)Ultra-rare · AF 0.00021%
cDNA changec.460+1G>A
ClinVar variantNM_006005.3(WFS1):c.460+1G>A
ClinVar accessionVCV000004515
Last evaluated2024/10/23 00:00

Observed at very low frequency in gnomAD.

Therapeutic Strategy Handoff · prediction

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Download the c.460+1G>A card below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals matched to this S2 splice variant and its domain context.

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Full Variant Card

c.460+1G_A — WFS1 Molecular Atlas Card

Variant type: Splice site Boundary: donor (5' splice site) · intronic offset +1 Nearest protein position: ~154 (N-terminal cytoplasmic (intrinsically disordered))

Schema category: S2 — Predicted frameshift skip of exon 4 (145 nt)

SpliceAI predicts strong donor (5') loss (ΔS 1.00) -> skipping of exon 4 (145 nt, NOT divisible by 3), which shifts the reading frame downstream. A premature stop is predicted at ~aa 115. The frameshifted/truncated product follows the frameshift schema (F1/F2 by NMD); typically too compromised for chaperone rescue — gene-therapy track. (acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.96, donor-loss 1.00.)

Splice prediction

  • Affected site: donor (5' splice site), canonical (±1/±2 core)
  • SpliceAI delta scores (GRCh38 chr4:6289132 G>A):
    • acceptor gain 0.00 · acceptor loss 0.00
    • donor gain 0.96 · donor loss 1.00
  • Predicted outcome: Predicted frameshift skip of exon 4 (145 nt)

Clinical evidence

  • Classification: Pathogenic
  • Review status: criteria provided, multiple submitters, no conflicts
  • cDNA change: c.460+1G>A
  • ClinVar accession: VCV000004515
  • Last evaluated: 2024/10/23 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (splice pipeline) on 2026-06-08T07:50:33.326616Z. Schema: reference/card_schema_extension.md (S1–S3). WFS1: UniProt O76024, AlphaFold v6.