TP53c.375+13G>AUncertain significance

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Variant interpretation report

TP53 c.375+13G>A, p.?

NM_000546.6:c.375+13G>A 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

Condition: Li-Fraumeni syndrome
Inheritance: Autosomal dominant
Evidence used: 2 supporting (benign) · 1 supporting (pathogenic)
Expert rules: ClinGen TP53 VCEP v2.4
Other laboratories (ClinVar): 5 Likely benign
Pipeline record: 27 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PM2 (supporting): This variant is extremely rare in population databases. gnomAD v4.1 total allele frequency is 3.72 x 10^-6 (6/1,612,114 alleles), well below the TP53 VCEP PM2_Supporting threshold of 0.003%. In the European (non-Finnish) subpopulation, frequency is 5.08 x 10^-6 (6/1,179,994 alleles), below the 0.004% threshold for subpopulations with multiple alleles.
BP4 (supporting): SpliceAI predicts no splicing impact (max delta = 0.02). Per the TP53 VCEP v2.4, intronic variants outside +/-1,2 positions with SpliceAI ≤ 0.1 meet BP4_Supporting. Multiple lines of computational evidence suggest this variant does not alter splicing.
BP7 (supporting): This is an intronic variant at +13 position (beyond +7 from the exon-intron boundary) with SpliceAI max delta = 0.02, predicting no impact on splicing. Per the TP53 VCEP v2.4, intronic variants at or beyond +7 with SpliceAI ≤ 0.1 meet BP7_Supporting.

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. 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

This variant is extremely rare in population databases. gnomAD v4.1 total allele frequency is 3.72 x 10^-6 (6/1,612,114 alleles), well below the TP53 VCEP PM2_Supporting threshold of 0.003%. In the European (non-Finnish) subpopulation, frequency is 5.08 x 10^-6 (6/1,179,994 alleles), below the 0.004% threshold for subpopulations with multiple alleles.

Benign criteria applied · 2

BP4Supporting

BP4 · supporting

SpliceAI predicts no splicing impact (max delta = 0.02). Per the TP53 VCEP v2.4, intronic variants outside +/-1,2 positions with SpliceAI ≤ 0.1 meet BP4_Supporting. Multiple lines of computational evidence suggest this variant does not alter splicing.

BP7Supporting

BP7 · supporting

This is an intronic variant at +13 position (beyond +7 from the exon-intron boundary) with SpliceAI max delta = 0.02, predicting no impact on splicing. Per the TP53 VCEP v2.4, intronic variants at or beyond +7 with SpliceAI ≤ 0.1 meet BP7_Supporting.

Recorded classification: Uncertain significance

ClinGen TP53 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TP53 Version 2.4 v2.4 point-based framework: PM2 supporting (+1) + BP4 supporting benign (-1) + BP7 supporting benign (-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

6 / 1,612,114 alleles

gnomAD v4.1: 6 / 1,612,114 alleles. Recorded AF 3.72182e-06. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.99351e-06; MAF= 0.00040%, 1/250406 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000163399; MAF= 0.01634%, 1/6120 alleles, homozygotes = 0).

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

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

SpliceAI score

0.020 maximum delta

Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗

ClinVar submissions

5 reported laboratory submissions

5 Likely benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

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, with the data and sources behind each one.

29 criteria with recorded statuses: 3 met · 9 not met · 1 not assessed · 16 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_000546.6:c.375+13G>A is an intronic variant in TP53 at position +13 of intron 4, outside the canonical splice consensus sequence.

This variant is extremely rare in population databases, with an allele frequency of 3.72 x 10^-6 in gnomAD v4.1 (6/1,612,114 alleles), meeting TP53 VCEP PM2_Supporting.

SpliceAI predicts no splicing impact (max delta = 0.02), meeting TP53 VCEP BP4_Supporting and BP7_Supporting for intronic variants at or beyond +7 with SpliceAI ≤ 0.1.

This variant has been reported in ClinVar as Likely benign by 5 clinical laboratories (ClinVar ID 379461), though review status is 1-star (criteria provided, single submitter) and no 3-star expert panel classification exists.

No functional data, segregation analysis, de novo observations, or case-control studies are available for this variant. The variant does not alter a protein-coding residue and is not eligible for PVS1, PS1, PS3, PM1, PM5, or BS3 under the TP53 VCEP framework.

Under the TP53 VCEP v2.4 point-based system, applying PM2_Supporting (+1), BP4_Supporting (-1), and BP7_Supporting (-1) yields a total of -1 points. Per the VCEP caveat, when at least 2 benign evidence codes are applied and PM2_Supporting is the only pathogenic code, the classification may be overridden to Likely Benign.

Met · 3

PM2 SupportingThis variant is extremely rare in population databases. gnomAD v4.1 total allele frequency is 3.72 x 10^-6 (6/1,612,114 alleles), well below the TP53 VCEP PM2_Supporting threshold of 0.003%. In the European (non-Finnish) subpopulation, frequency is 5.08 x 10^-6 (6/1,179,994 alleles), below the 0.004% threshold for subpopulations with multiple alleles. Details ▾Hide ▴

Evidence considered

gnomAD v4.1: total AF = 3.72e-06 (6/1
612
114)
NFE AF = 5.08e-06 (6/1
179
994)
grpmax FAF = 1.83e-06. gnomAD v2.1: total AF = 3.99e-06 (1/250
406)
allele in 'Remaining' population only (excluded per VCEP).

Still missing

VAF/allele balance data for the 6 NFE alleles in gnomAD v4.1 not inspected
if majority have VAF < 0.35
CHIP contamination cannot be excluded.

Sources

gnomad_v4 ↗cspec ↗

BP4 SupportingSpliceAI predicts no splicing impact (max delta = 0.02). Per the TP53 VCEP v2.4, intronic variants outside +/-1,2 positions with SpliceAI ≤ 0.1 meet BP4_Supporting. Multiple lines of computational evidence suggest this variant does not alter splicing. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.02 ≤ 0.1
meets TP53 VCEP BP4_Supporting threshold for intronic variants. No predicted donor/acceptor gain or loss.

Sources

spliceai ↗cspec ↗vcep_pp3_bp4_codes

BP7 SupportingThis is an intronic variant at +13 position (beyond +7 from the exon-intron boundary) with SpliceAI max delta = 0.02, predicting no impact on splicing. Per the TP53 VCEP v2.4, intronic variants at or beyond +7 with SpliceAI ≤ 0.1 meet BP7_Supporting. Details ▾Hide ▴

Evidence considered

Variant position: intron 4
+13 from the exon 4 donor site (beyond +7 cutoff). SpliceAI max delta = 0.02 ≤ 0.1. BP4 is also met. No requirement for nucleotide conservation assessment per Walker et al.
2023 (PMID: 37352859).

Sources

spliceai ↗cspec ↗vcep_pp3_bp4_codes

Not met · 9 · evaluated, threshold not reached

PS2 No de novo observation has been reported for this variant. No proband data with confirmed maternity and paternity is available in ClinVar, the literature, or any case-level evidence source. Details ▾Hide ▴

Evidence considered

ClinVar submissions are all Likely benign from clinical laboratories
no de novo reports identified. No literature case reports with parental confirmation.

Still missing

No proband-level data available
no family studies reported.

Sources

clinvar ↗

PS4 No case-control data or proband counting is available for this variant. No Li-Fraumeni syndrome-affected probands with this variant have been reported. The TP53 VCEP PS4 point system requires documented probands with LFS-associated cancers; none are available. Details ▾Hide ▴

Evidence considered

Variant is reported as Likely benign in ClinVar by 5 clinical laboratories with no associated phenotype detail. No proband-level data with cancer phenotype or case-control enrichment.

Still missing

No proband cancer data
no case-control studies including this variant.

Sources

clinvar ↗

PP1 No cosegregation data is available for this variant. The TP53 VCEP PP1 requires observation in 3-4 meioses for supporting, 5-6 for moderate, and ≥7 for strong. No family studies or cosegregation analysis has been reported. Details ▾Hide ▴

Evidence considered

No family-based cosegregation data in ClinVar submissions
literature
or any evidence source.

Still missing

No family studies available.

PP3 SpliceAI predicts no significant splicing impact (max delta score = 0.02). The TP53 VCEP PP3 threshold for intronic variants outside +/-1,2 positions is SpliceAI ≥ 0.2, which is not met. No other in silico evidence supports pathogenicity for this deep intronic variant. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.02
far below the VCEP PP3 cutoff of ≥0.2 for intronic variants. No REVEL
BayesDel
or HCI prior scores available for a non-coding variant.

Sources

spliceai ↗cspec ↗

PP4 The TP53 VCEP PP4 requires observation of the variant with variant allele fraction (VAF) of 5-35%, suggesting somatic mosaicism in a patient with a phenotype specific for TP53-related disease. No VAF data is available for any carrier of this variant, and no phenotype description is provided in ClinVar submissions. Details ▾Hide ▴

Evidence considered

ClinVar Likely benign submissions provide no VAF data and no phenotype details
no clinical case reports with VAF measurement exist.

Still missing

No VAF data available
no proband phenotype reports.

Sources

clinvar ↗cspec ↗

BA1 The gnomAD v4.1 grpmax filtering allele frequency is 1.83 x 10^-6, far below the TP53 VCEP BA1 threshold of ≥0.001 (0.1%). This variant is not common enough in any population to qualify as a stand-alone benign polymorphism. Details ▾Hide ▴

Evidence considered

gnomAD v4.1 grpmax FAF = 1.83e-06
well below the 0.001 BA1 cutoff. No subpopulation has ≥2 alleles with AF ≥ 0.001.

Sources

gnomad_v4 ↗cspec ↗

BS1 The gnomAD v4.1 grpmax filtering allele frequency is 1.83 x 10^-6, far below the TP53 VCEP BS1 threshold of ≥0.0003 (0.03%). The variant is too rare in population databases to meet BS1. Details ▾Hide ▴

Evidence considered

gnomAD v4.1 grpmax FAF = 1.83e-06
well below the 0.0003 BS1 cutoff. No subpopulation has ≥2 alleles with AF ≥ 0.0003.

Sources

gnomad_v4 ↗cspec ↗

BS2 The TP53 VCEP BS2 requires ≥2 unrelated females aged ≥60 without cancer from a single source. No such observational data is available for this variant. No healthy elderly female carriers have been documented. Details ▾Hide ▴

Evidence considered

No data on elderly female carriers
ClinVar provides no phenotype data for the 5 clinical laboratory submissions.

Still missing

No healthy elderly carrier data available from any source.

BS4 No segregation data is available to assess lack of cosegregation with LFS-associated cancers. The TP53 VCEP BS4 requires observed lack of segregation in affected family members; no family studies exist for this variant. Details ▾Hide ▴

Evidence considered

No family segregation studies reported for this variant.

Still missing

No family-based segregation data available.

Not assessed · 1 · no assessment recorded

PS5 PS5 is not in the active ACMG/AMP 2015 criteria set for this adjudication. Details ▾Hide ▴

No further detail was recorded.

Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/AIntronic variant at +13 position, beyond the canonical +/-1,2 splice donor/acceptor sites. PVS1 per the TP53 VCEP v2.4 applies to nonsense, frameshift, canonical splice sites (+/-1,2), initiation codon, and exon-level deletions. This variant does not fall within any PVS1-eligible variant bucket. Details ▾Hide ▴

Evidence considered

Variant is c.375+13G>A
an intronic substitution at +13 in intron 4
not a canonical splice site
SpliceAI max delta = 0.02 confirms no predicted splicing impact.

Sources

pvs1_generic_framework ↗vcep_pvs1_flowchartvcep_pvs1_splicing_worksheet

PS1 N/APS1 applies to nucleotide changes at the same position predicted to cause the same amino acid change as a known pathogenic missense variant. This is an intronic variant with no amino acid change (NP_000537.3:p.?); no same-residue missense comparator is possible. Details ▾Hide ▴

Evidence considered

Intronic variant at +13
no protein consequence
variant class is not missense.

PS3 N/AThe TP53 VCEP v2.4 functional assay framework (Kato, Funk, Giacomelli, Kotler, Kawaguchi) applies only to missense variants and small in-frame deletions. This intronic variant at +13 has no amino acid change and is not eligible for the VCEP functional assessment. No other functional data specific to this non-coding variant exists. Details ▾Hide ▴

Evidence considered

Variant is intronic
functional assays are designed for coding missense/in-frame deletions. Not listed in Functional-worksheet.xlsx.

Sources

vcep_functional_worksheetvcep_flowchart_for_application_of_functional_rule_codes

PM1 N/AThe TP53 VCEP v2.4 PM1 applies to missense variants at specific hotspot codons (175, 245, 248, 249, 273, 282 on NM_000546.4) or cancerhotspots.org entries with ≥2 somatic occurrences. This is an intronic variant at +13, not a missense change at any of the designated codons, and is not listed at cancerhotspots.org. Details ▾Hide ▴

Evidence considered

Intronic variant at +13
not a missense variant
no codon position is affected.

Sources

cspec ↗

PM3 VCEPRecessive disorder criterion — not applicable to autosomal dominant TP53-associated Li-Fraumeni syndrome. Details ▾Hide ▴

No further detail was recorded.

PM4 VCEPProtein length change due to in-frame deletion/insertion — not applicable to a substitution variant. Details ▾Hide ▴

No further detail was recorded.

PM5 N/APM5 requires a missense variant at the same amino acid residue as a known pathogenic missense variant. This intronic variant has no amino acid change (NP_000537.3:p.?) and is not eligible for same-residue missense PM5 assessment. Details ▾Hide ▴

Evidence considered

Variant class is not missense
no amino acid residue affected
pm5_candidates.json confirms not eligible.

Sources

pm5_candidates

PM6 VCEPThe TP53 VCEP v2.4 designates PM6 as Not Applicable. Additionally, no de novo observation with confirmed maternity and paternity is reported for this variant. Details ▾Hide ▴

Evidence considered

VCEP designation: Not Applicable.

Sources

cspec ↗

PP2 VCEPThe TP53 VCEP v2.4 designates PP2 as Not Applicable. PP2 (missense variant in a gene with low rate of benign missense variation) is not used under this VCEP framework. Details ▾Hide ▴

Evidence considered

VCEP designation: Not Applicable.

Sources

cspec ↗

PP5 VCEPThe TP53 VCEP v2.4 designates PP5 as Not Applicable. ClinVar review status is 'criteria provided, single submitter' (1-star), which does not meet the 3-star expert panel threshold required for the global PP5 override. PP5 is not applied under this framework. Details ▾Hide ▴

Evidence considered

VCEP designation: Not Applicable. ClinVar 1-star review status
no 3-star expert panel classification available for the PP5/BP6 global override.

Sources

cspec ↗clinvar ↗

BS3 N/AThe TP53 VCEP v2.4 BS3 functional assay framework applies only to missense variants and small in-frame deletions. This intronic variant has no amino acid change and is not eligible for VCEP functional assessment. Details ▾Hide ▴

Evidence considered

Intronic variant
functional assays are designed for coding missense/in-frame deletions only.

Sources

vcep_functional_worksheetvcep_flowchart_for_application_of_functional_rule_codes

BP1 VCEPThe TP53 VCEP v2.4 designates BP1 as Not Applicable. BP1 (missense variant in a gene where primarily truncating variants cause disease) does not apply to TP53, where both missense and truncating variants contribute to disease. Details ▾Hide ▴

Evidence considered

VCEP designation: Not Applicable.

Sources

cspec ↗

BP2 VCEPThe TP53 VCEP v2.4 designates BP2 as Not Applicable. BP2 (observed in trans with a pathogenic variant) is not applicable to autosomal dominant TP53-associated Li-Fraumeni syndrome. Details ▾Hide ▴

Evidence considered

VCEP designation: Not Applicable.

Sources

cspec ↗

BP3 VCEPIn-frame deletion/insertion in a repetitive region — not applicable to a substitution variant. Details ▾Hide ▴

No further detail was recorded.

BP5 VCEPThe TP53 VCEP v2.4 designates BP5 as Not Applicable. BP5 (variant found in a case with an alternate molecular basis for disease) is not used under this VCEP framework. Details ▾Hide ▴

Evidence considered

VCEP designation: Not Applicable.

Sources

cspec ↗

BP6 VCEPThe TP53 VCEP v2.4 designates BP6 as Not Applicable. ClinVar review status is 'criteria provided, single submitter' (1-star), which does not meet the 3-star expert panel threshold required for the global BP6 override. BP6 is not applied under this framework. Details ▾Hide ▴

Evidence considered

VCEP designation: Not Applicable. ClinVar 1-star review status
no 3-star expert panel benign classification available.

Sources

cspec ↗clinvar ↗

Identifiers

Gene: TP53
Transcript: NM_000546.6
Coding (HGVS c.): NM_000546.6:c.375+13G>A
Protein (HGVS p.): NP_000537.3:p.?
GRCh38: chr17:7675981 C>T
GRCh37: chr17:7579299 C>T
ClinVar: 379461

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

—

Transcript span

—

Strand

—

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 6 / 1,612,114 alleles AF 3.72e-06 · 0 homozygotes · FAF 1.83e-06

gnomAD v2.1 1 / 250,406 alleles AF 3.99e-06 · 0 homozygotes

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 3.7e-06 · 6 / 1,612,114 alleles · 0 hom · FAF 1.8e-06

European (non-Finnish)6 / 1,179,994

5.1e-06

0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 4e-06 · 1 / 250,406 alleles · 0 hom

Remaining individuals1 / 6,120

0.00016

0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 3.72182e-06; MAF= 0.00037%, 6/1612114 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.08477e-06; MAF= 0.00051%, 6/1179994 alleles, homozygotes = 0); grpmax FAF= 1.83e-06.

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +87 bp

0.010

SpliceAI acceptor gainat +272 bp

0.000

SpliceAI donor lossat -96 bp

0.020

SpliceAI donor gainat +29 bp

0.000

Pangolin splice lossmagnitude shown

-0.010

Pangolin splice gain

0.020

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta = 0.02 ≤ 0.1
meets TP53 VCEP BP4_Supporting threshold for intronic variants. No predicted donor/acceptor gain or loss.

Sources

spliceai ↗cspec ↗vcep_pp3_bp4_codes

Evidence considered

Variant position: intron 4
+13 from the exon 4 donor site (beyond +7 cutoff). SpliceAI max delta = 0.02 ≤ 0.1. BP4 is also met. No requirement for nucleotide conservation assessment per Walker et al.
2023 (PMID: 37352859).

Sources

spliceai ↗cspec ↗vcep_pp3_bp4_codes

Evidence considered

SpliceAI max delta = 0.02
far below the VCEP PP3 cutoff of ≥0.2 for intronic variants. No REVEL
BayesDel
or HCI prior scores available for a non-coding variant.

Sources

spliceai ↗cspec ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).

7 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Joint consensus recommendation from ACMG and AMP providing standards and guidelines for interpretation of sequence variants. Describes the general ACMG/AMP classification framework including criteria definitions and strength levels.
Does not name this variant
PMID 25741868 ↗
Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.

Trepanier A et al. · 2004

Practice recommendations from the National Society of Genetic Counselors for cancer genetic risk assessment and counseling. Describes hereditary cancer syndromes including Li-Fraumeni syndrome (TP53) at the syndrome level.
Does not name this variant
PMID 15604628 ↗
Li-Fraumeni Syndrome.

Adam MP et al. · 1993

GeneReviews entry for Li-Fraumeni Syndrome. Summarizes clinical characteristics, diagnosis, and management of LFS, including TP53 as the causative gene.
Does not name this variant
PMID 20301488 ↗
ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

Green RC et al. · 2013

ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing. Includes TP53 among the list of genes for which incidental findings should be reported.
Does not name this variant
PMID 23788249 ↗
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

Hampel H et al. · 2015

Joint practice guideline from ACMG and NSGC providing referral indications for cancer predisposition assessment. Includes Li-Fraumeni syndrome criteria (adrenocortical tumor, choroid plexus carcinoma, multiple LFS-associated cancers).
Does not name this variant
PMID 25394175 ↗
Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents.

Points to consider regarding ethical, legal, and psychosocial implications of genetic testing in children and adolescents. General ethics guidance, not variant-specific.
Does not name this variant
PMID 26140447 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Describes an evidence-based classification system but does not address this specific TP53 variant.
Does not name this variant
PMID 28492532 ↗

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

gnomAD v4.1 6 / 1,612,114 recorded alleles Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.020 Open source ↗

ClinVar 5 Likely benign 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

gnomAD v2.1

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (5 clinical laboratories). (ClinVarID = 379461)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).

Somatic

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