TP53c.-29+102T>GUncertain significance

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Variant interpretation report

TP53 c.-29+102T>G, p.?

NM_000546.6:c.-29+102T>G NP_000537.3:p.? View identifiers

Classification

Uncertain significance

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About TP53

No gene-level summary was recorded for this case.

Key facts

Evidence used: 2 supporting (benign) · 1 supporting (pathogenic)
Expert rules: ClinGen TP53 VCEP v2.4.0
Pipeline record: 1 Jul 2026 · version 7.0.1

Evidence considered

View criteria

Applied evidence criteria

PM2 (supporting): NM_000546.6:c.-29+102T>G is absent from both gnomAD v2.1 and v4.1, meeting the VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%).
BP4 (supporting): SpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00, which is ≤0.1), meeting the VCEP BP4_Supporting threshold for intronic variants.
BP7 (supporting): NM_000546.6:c.-29+102T>G is an intronic variant at position +102 (beyond +7) with SpliceAI max delta score of 0.00 (≤0.1), meeting the VCEP BP7_Supporting rule for intronic variants at or beyond +7 to -21 positions with no predicted splice impact.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is ClinGen TP53 VCEP v2.4.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 1 Benign evidence criteria: 2

Pathogenic criteria applied · 1

PM2Supporting

PM2 · supporting

NM_000546.6:c.-29+102T>G is absent from both gnomAD v2.1 and v4.1, meeting the VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%).

Benign criteria applied · 2

BP4Supporting

BP4 · supporting

SpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00, which is ≤0.1), meeting the VCEP BP4_Supporting threshold for intronic variants.

BP7Supporting

BP7 · supporting

NM_000546.6:c.-29+102T>G is an intronic variant at position +102 (beyond +7) with SpliceAI max delta score of 0.00 (≤0.1), meeting the VCEP BP7_Supporting rule for intronic variants at or beyond +7 to -21 positions with no predicted splice impact.

Recorded classification: Uncertain significance

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.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗

ClinVar submissions

Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗

No screenshot for this evidence

Functional evidence

Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗

Somatic evidence

No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Context only COSMIC ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen TP53 VCEP v2.4.0, with the data and sources behind each one.

26 criteria with recorded statuses: 3 met · 3 not met · 6 not assessed · 14 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

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).

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).

VCEP Tavtigian point tally: PM2_Supporting (+1), BP4_Supporting (−1), BP7_Supporting (−1) = −1, which falls in the VUS range (−1 to 5).

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.

No publications identified for this variant; absent from ClinVar and COSMIC.

Met · 3

PM2 SupportingNM_000546.6:c.-29+102T>G is absent from both gnomAD v2.1 and v4.1, meeting the VCEP PM2_Supporting threshold of allele frequency <0.00003 (0.003%). Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 (0 alleles)
Absent from gnomAD v4.1 (0 alleles)

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP4 SupportingSpliceAI predicts no splicing impact for this intronic variant (max delta score = 0.00, which is ≤0.1), meeting the VCEP BP4_Supporting threshold for intronic variants. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.00
no predicted splicing impact
meeting VCEP BP4_Supporting threshold of ≤0.1

Sources

spliceai ↗cspec ↗

BP7 SupportingNM_000546.6:c.-29+102T>G is an intronic variant at position +102 (beyond +7) with SpliceAI max delta score of 0.00 (≤0.1), meeting the VCEP BP7_Supporting rule for intronic variants at or beyond +7 to -21 positions with no predicted splice impact. Details ▾Hide ▴

Evidence considered

Intronic variant at +102 in intron 1 (beyond +7)
SpliceAI max delta score = 0.00
no predicted splicing impact
meeting VCEP BP7_Supporting threshold of ≤0.1

Sources

spliceai ↗cspec ↗

Not met · 3 · evaluated, threshold not reached

PP3 VCEP PP3 for intronic variants requires SpliceAI ≥0.2. This variant has a SpliceAI max delta score of 0.00, indicating no predicted splicing impact. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.00
does not meet VCEP PP3 threshold of ≥0.2

Sources

spliceai ↗cspec ↗

BA1 VCEP BA1 requires a filtering allele frequency ≥0.001 (0.1%) in a gnomAD continental subpopulation. This variant is absent from gnomAD and does not meet the BA1 threshold. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1
does not meet BA1 threshold of ≥0.1%

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 VCEP BS1 requires a filtering allele frequency ≥0.0003 (0.03%) but <0.001 in a gnomAD continental subpopulation. This variant is absent from gnomAD and does not meet the BS1 threshold. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1
does not meet BS1 threshold of ≥0.03%

Sources

gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 6 · no assessment recorded

PS2 No de novo data or proband information is available for this variant. The VCEP PS2 point system requires proband cancer phenotype data, which has not been provided. Details ▾Hide ▴

Still missing

No proband or de novo data available

PS4 No proband prevalence data is available. The variant is absent from ClinVar, and no LFS-associated cancer phenotype data has been provided to apply the VCEP PS4 point system. Details ▾Hide ▴

Evidence considered

Variant absent from ClinVar
no proband data available

Still missing

No proband cancer phenotype data available for PS4 point tally

Sources

clinvar ↗

PP1 No cosegregation data is available for this variant. The VCEP PP1 point system requires meiotic segregation data across families, which has not been provided. Details ▾Hide ▴

Still missing

No cosegregation data available

PP4 The VCEP PP4 rule requires VAF data (5-35%) from patient observations. No VAF or patient phenotype information has been provided for this variant. Details ▾Hide ▴

Still missing

No VAF or patient phenotype data available

BS2 VCEP BS2 requires observations in older unaffected females (≥60 years without cancer). No such data is available for this variant. Details ▾Hide ▴

Still missing

No data on older unaffected females available

BS4 VCEP BS4 requires lack of segregation in affected family members with LFS-associated cancers. No segregation data is available for this variant. Details ▾Hide ▴

Still missing

No segregation data available

Not applicable · 14· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_000546.6:c.-29+102T>G is an intronic variant located at +102 in intron 1, outside the canonical ±1,2 splice consensus. It does not fall into any of the TP53 VCEP PVS1 null-variant buckets (nonsense, frameshift, canonical splice site, initiation codon, exon deletion, CNV). Details ▾Hide ▴

Evidence considered

Intronic variant at +102 in intron 1
not at canonical ±1
2 splice positions
Variant class is 'other'
not covered by VCEP PVS1 decision tree

Sources

pvs1_variant_assessmentvcep_pvs1_flowchart

PS1 N/APS1 requires a missense variant with the same amino acid change as an established pathogenic variant. This is an intronic variant with no amino acid consequence. Details ▾Hide ▴

Evidence considered

Intronic variant
no amino acid change

PS3 N/AVCEP PS3/BS3 functional rules apply to missense variants and small in-frame deletions only. This intronic variant is not covered by the functional assay framework and was not found in the VCEP Functional-worksheet.xlsx. Details ▾Hide ▴

Evidence considered

VCEP functional rules restricted to missense and in-frame deletions
Variant not present in Functional-worksheet.xlsx

Sources

vcep_functional_worksheetvcep_flowchart_for_application_of_functional_rule_codes

PM1 N/AVCEP PM1 applies to missense variants within hotspot codons (175, 245, 248, 249, 273, 282) or with ≥2 somatic occurrences at cancerhotspots.org for the same amino acid change. This is an intronic variant with no amino acid change. Details ▾Hide ▴

Evidence considered

Intronic variant
no amino acid residue applicable for hotspot assessment

Sources

cspec ↗

PM5 N/APM5 requires a missense variant at an amino acid residue where a different pathogenic missense change has been established. This is an intronic variant with no amino acid consequence. Details ▾Hide ▴

Evidence considered

Intronic variant
not eligible for same-residue missense comparison

Sources

pm5_candidates

PM6 VCEPPM6 is marked as Not Applicable by the TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴

Evidence considered

VCEP specification marks PM6 as not applicable

Sources

cspec ↗

PP2 VCEPPP2 is marked as Not Applicable by the TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴

Evidence considered

VCEP specification marks PP2 as not applicable

Sources

cspec ↗

PP5 VCEPPP5 is marked as Not Applicable by the TP53 VCEP v2.4.0 specifications, as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴

Evidence considered

VCEP specification marks PP5 as not applicable

Sources

cspec ↗

BS3 N/AVCEP BS3 functional rules apply to missense variants and small in-frame deletions only. This intronic variant is not covered by the functional assay framework. Details ▾Hide ▴

Evidence considered

VCEP functional rules restricted to missense and in-frame deletions

Sources

vcep_functional_worksheetvcep_flowchart_for_application_of_functional_rule_codes

BP1 VCEPBP1 is marked as Not Applicable by the TP53 VCEP v2.4.0 specifications; truncating variants account for only a portion of disease-causing variants in TP53. Details ▾Hide ▴

Evidence considered

VCEP specification marks BP1 as not applicable

Sources

cspec ↗

BP2 VCEPBP2 is marked as Not Applicable by the TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴

Evidence considered

VCEP specification marks BP2 as not applicable

Sources

cspec ↗

BP5 VCEPBP5 is marked as Not Applicable by the TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴

Evidence considered

VCEP specification marks BP5 as not applicable

Sources

cspec ↗

BP6 VCEPBP6 is marked as Not Applicable by the TP53 VCEP v2.4.0 specifications, as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴

Evidence considered

VCEP specification marks BP6 as not applicable

Sources

cspec ↗

PS5 N/APS5 is not a criterion in the TP53 VCEP v2.4.0 specifications and is not included in the standard ACMG/AMP 2015 framework. Details ▾Hide ▴

Evidence considered

PS5 is not a recognized ACMG/AMP criterion

Identifiers

Gene: TP53
Transcript: NM_000546.6
Coding (HGVS c.): NM_000546.6:c.-29+102T>G
Protein (HGVS p.): NP_000537.3:p.?
GRCh38: chr17:7687275 A>C
GRCh37: chr17:7590593 A>C

Gene diagram

Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.6. Select a row to find it on the plot.

TP53NM_000546.6

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in TP53 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 Allele count data not recorded

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -434 bp

0.000

SpliceAI acceptor gainat -422 bp

0.000

SpliceAI donor lossat -21 bp

0.000

SpliceAI donor gainat +183 bp

0.000

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta score = 0.00
no predicted splicing impact
meeting VCEP BP4_Supporting threshold of ≤0.1

Sources

spliceai ↗cspec ↗

Evidence considered

Intronic variant at +102 in intron 1 (beyond +7)
SpliceAI max delta score = 0.00
no predicted splicing impact
meeting VCEP BP7_Supporting threshold of ≤0.1

Sources

spliceai ↗cspec ↗

PP3 VCEP PP3 for intronic variants requires SpliceAI ≥0.2. This variant has a SpliceAI max delta score of 0.00, indicating no predicted splicing impact. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.00
does not meet VCEP PP3 threshold of ≥0.2

Sources

spliceai ↗cspec ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar Captured ClinVar source record Open source ↗

COSMIC Captured COSMIC source record Open source ↗

ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant is absent from ClinVar.

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Somatic

This variant has not previously been reported in somatic cancers (COSMIC).