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c.315+11C>T

SpliceS3Likely benignCytoplasmic · predicted
Splice variant · splice site near at position 105 · 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 105 (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 donor (5') 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/Likely benign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsAutosomal dominant nonsyndromic hearing loss 6; WFS1-Related Spectrum Disorders; Wolfram syndrome 1
Population frequency (gnomAD v4)Ultra-rare · AF 0.0028%
cDNA changec.315+11C>T
ClinVar variantNM_006005.3(WFS1):c.315+11C>T
ClinVar accessionVCV000349311
Last evaluated2026/01/05 00:00

Observed at very low frequency in gnomAD.

Classified for2★ documented assertion

ClinVar classifies this variant as Benign/Likely benign for Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related spectrum (unresolved mode) (dominant or recessive); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). ClinVar records this under a WFS1-spectrum label that spans both disease families — recessive Wolfram syndrome (biallelic) and the dominant WFS1-related disorders. The label does not resolve which applies, and it is not a severity statement.

  • Nonsyndromic hearing loss (DFNA6/14/38)autosomal dominant · OMIM 600965submitted as: Autosomal dominant nonsyndromic hearing loss 6
  • WFS1-related spectrum (unresolved mode)dominant or recessivesubmitted as: WFS1-Related Spectrum Disorders
  • 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)
AF 0.0028% · 43 / 1,553,910 alleles
Homozygotes
0
Highest-frequency population
East Asian · AF 0.026%

Highest in East Asian: AF 0.026% (11 of 41,872 alleles), 9.5x the global figure. The global AF describes the general population, not the at-risk group.

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.
East Asian0.026%11 / 41,8720~1 in 1900
Admixed American0.016%8 / 51,0760~1 in 3190
South Asian0.0071%6 / 84,3640~1 in 7030
Remaining individuals0.0033%2 / 60,1580~1 in 15040
African / African American · under-sampled0.0014%1 / 73,6680—
European (non-Finnish)0.0013%15 / 1,147,8100~1 in 38260

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.315+11C>T 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.315+11C_T — WFS1 Molecular Atlas Card

Variant type: Splice site Boundary: donor (5' splice site) · intronic offset +11 Nearest protein position: ~105 (N-terminal cytoplasmic (intrinsically disordered))

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

SpliceAI predicts little splicing disruption at this donor (5') 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: donor (5' splice site), extended splice region
  • SpliceAI delta scores (GRCh38 chr4:6287186 C>T):
    • 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/Likely benign — for Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related spectrum (unresolved mode) (dominant or recessive); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)

ClinVar classifies this variant as Benign/Likely benign for Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related spectrum (unresolved mode) (dominant or recessive); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). ClinVar records this under a WFS1-spectrum label that spans both disease families — recessive Wolfram syndrome (biallelic) and the dominant WFS1-related disorders. The label does not resolve which applies, and it is not a severity statement.

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/Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Autosomal dominant nonsyndromic hearing loss 6; WFS1-Related Spectrum Disorders; Wolfram syndrome 1
  • cDNA change: c.315+11C>T
  • ClinVar accession: VCV000349311
  • Last evaluated: 2026/01/05 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (splice pipeline) on 2026-06-08T07:49:51.998247Z. Schema: reference/card_schema_extension.md (S1–S3). WFS1: UniProt O76024, AlphaFold v6.