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c.316-14T>G

SpliceS3BenignCytoplasmic · predicted
Splice variant · splice site near at position 106 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

S3 — Minimal predicted splicing impact (SpliceAI ΔS 0.00)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 106 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted.

Variant Assessment

Variant type
Splice
Schema
S3
Minimal predicted splicing impact (SpliceAI ΔS 0.00)
Domain
N-terminal cytoplasmic (intrinsically disordered)
Status
—

Therapeutic Implication · S3

SpliceAI predicts little splicing disruption at this acceptor (3') site (max ΔS 0.00 < 0.2; acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.00, 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, single submitter
Associated conditionsWolfram syndrome 1
Population frequency (gnomAD v4)Ultra-rare · AF 0.00014%
cDNA changec.316-14T>G
ClinVar variantNM_006005.3(WFS1):c.316-14T>G
ClinVar accessionVCV001810333
Last evaluated1/01/01 00:00

Observed at very low frequency in gnomAD.

Classified for1★ unverified submission

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
  • This rests on a single submitter (1★). Treat the conditions above as submitted, not as documented phenotypes.
  • 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: 1★ single submitter. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.

Population frequency
Global (all ancestries)
AF 0.00014% · 2 / 1,453,900 alleles
Homozygotes
0
Highest-frequency population
European (non-Finnish) · AF 0.00018%

Highest in European (non-Finnish): AF 0.00018% (2 of 1,108,910 alleles), in line with the global figure.

No homozygotes reported in gnomAD v4. For a recessive allele this is expected and is not, on its own, evidence either way.

Ancestry groupAllele freq.AC / ANHom.Carrier est.
European (non-Finnish)0.00018%2 / 1,108,9100~1 in 277230

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.316-14T>G card below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals matched to this S3 splice variant and its domain context.

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Full Variant Card

c.316-14T_G — WFS1 Molecular Atlas Card

Variant type: Splice site Boundary: acceptor (3' splice site) · intronic offset -14 Nearest protein position: ~106 (N-terminal cytoplasmic (intrinsically disordered))

Schema category: S3 — Minimal predicted splicing impact (SpliceAI ΔS 0.00)

SpliceAI predicts little splicing disruption at this acceptor (3') site (max ΔS 0.00 < 0.2; acceptor-gain 0.00, acceptor-loss 0.00, donor-gain 0.00, 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: acceptor (3' splice site), extended splice region
  • SpliceAI delta scores (GRCh38 chr4:6288973 T>G):
    • acceptor gain 0.00 · acceptor loss 0.00
    • donor gain 0.00 · donor loss 0.00
  • Predicted outcome: Minimal predicted splicing impact (SpliceAI ΔS 0.00)

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.

This rests on a single submitter (1★). Treat the conditions above as submitted, not as documented phenotypes. 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, single submitter
  • Associated conditions: Wolfram syndrome 1
  • cDNA change: c.316-14T>G
  • ClinVar accession: VCV001810333
  • Last evaluated: 1/01/01 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (splice pipeline) on 2026-06-08T07:50:11.766402Z. Schema: reference/card_schema_extension.md (S1–S3). WFS1: UniProt O76024, AlphaFold v6.