# 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))

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## 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.)

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## 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)

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## 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

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_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._