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TP53
Final classification
VUS
TP53 c.-29+102T>G · p.?
TP53

NM_000546.6:c.-29+102T>G is an intronic variant in TP53 located at position +102 in intron 1.

Gene
TP53
Transcript
NM_000546.6
HGVS · transcript:coding
NM_000546.6:c.-29+102T>G
Consequence
N/A
GRCh38
chr17:7687275 A>C
GRCh37
chr17:7590593 A>C
Basis Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PM2 supporting (+1) + BP4 supporting (-1) + BP7 supporting (-1) = -1 points, which maps to VUS.
Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PM2 supporting (+1) + BP4 supporting (-1) + BP7 supporting (-1) = -1 points, which maps to VUS.
Classification rationale
PM2 BP4BP7 VUS
TP53 c.-29+102T>G

NM_000546.6:c.-29+102T>G is an intronic variant in TP53 located at position +102 in intron 1. This variant is absent from gnomAD v2.1 and v4.1 population databases, meeting PM2_Supporting per TP53 VCEP specifications (allele frequency <0.00003).1 SpliceAI predicts no impact on splicing (max delta score 0.00), meeting BP4_Supporting and BP7_Supporting per TP53 VCEP specifications (SpliceAI ≤0.1 for intronic variants).2 VCEP Tavtigian point tally: PM2_Supporting (+1), BP4_Supporting (−1), BP7_Supporting (−1) = −1, which falls in the VUS range (−1 to 5).3 Per the VCEP CAVEAT, a final point value of −1 is overridden to Likely Benign when at least two benign evidence codes are applied and PM2_Supporting is the only pathogenic code applied. With BP4_Supporting and BP7_Supporting as the two benign codes, this override applies.4 No publications identified for this variant; absent from ClinVar and COSMIC.

PM2 + BP4 + BP7 VUS
3 final_classification_framework
4 final_classification_framework
Gene diagram · NM_000546.6 · variants mapped to exon structure
TP53 NM_000546.6
Fetching transcript structure from UCSC…
Applied criteria · 3 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      Research & evidence
      Population frequency
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      v4.1
      Absent from gnomAD v4.1.
      v2.1
      Absent from gnomAD v2.1.
      🇨🇦 CA
      Absent from gnomAD-Canada v1.0.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD v4.1
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD v2.1
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD Canada 🇨🇦
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      ClinVar screenshot
      ClinVar
      This variant is absent from ClinVar.
      SpliceAI screenshot
      In silico
      SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Somatic evidence
      COSMIC
      This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      COSMIC ↗
      Sources & reference links
      8Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      gnomAD-Canada
      SpliceAI
      OncoKB
      COSMIC