About TP53
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TP53 c.509C>T, p.(Thr170Met)
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.
Words with a dotted underline have a short definition. Hover or tap them.
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
This variant is present at very low frequency in gnomAD v4.1 (total AF = 1.55e-05, 25/1,614,086 alleles, 0 homozygotes). The highest non-founder subpopulation frequency is South Asian at 3.29e-05 (3 alleles). All non-excluded genetic ancestry groups with multiple alleles have AF < 0.00004, and total AF < 0.00003, meeting the TP53 VCEP PM2_Supporting threshold.
Benign criteria applied · 2
BS3Supporting
BS3 · supporting
The TP53 VCEP Functional-worksheet.xlsx (Supplementary Table S3) assigns BS3_Supporting to p.Thr170Met. The variant is Partially functional in the Kato et al. (PMID:12826609) assay and demonstrates no loss of function (noLOF) across all available eligible assays (Funk, Giacomelli, Kotler). This satisfies the VCEP BS3_Supporting rule: Partially functional on Kato data AND no evidence of LOF by all available assays.
BP6Supporting
BP6 · supporting
Expert panel ClinGen TP53 Variant Curation Expert Panel, ClinGen classified as Likely benign.
Recorded classification: Uncertain significance
Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PM2 supporting (+1) + BS3 supporting (-1) = 0 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
25 / 1,614,086 alleles
gnomAD v4.1: 25 / 1,614,086 alleles. Recorded AF 1.54886e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.59842e-05; MAF= 0.00460%, 13/282706 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.74905e-05; MAF= 0.00775%, 10/129048 alleles, homozygotes = 0); grpmax FAF= 4.74e-05.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
9 reported laboratory submissions
5 Likely benign · 3 Uncertain significance · 1 Uncertain Significance.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
14 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52701457, n = 14 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
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 · 9 not met · 6 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000546.5:c.509C>T (p.Thr170Met) is a missense variant in exon 5 of TP53. This variant is present at very low frequency in gnomAD v4.1 (AF=1.55e-05, 25/1,614,086 alleles, 0 homozygotes), meeting PM2_Supporting per the TP53 VCEP specifications (total AF < 0.003%; no non-founder subpopulation with multiple alleles exceeds 0.004%).
Functional assay data from the TP53 VCEP Functional-worksheet.xlsx (Supplementary Table S3) demonstrates that p.Thr170Met is partially functional in the Kato et al. yeast transactivation assay and shows no loss of function across all available eligible assays (Funk, Giacomelli, Kotler), meeting BS3_Supporting per the VCEP functional rules.
In silico predictions were evaluated per the TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2), which assigns 'No evidence' for c.509C>T — neither PP3 nor BP4 is met. The variant has aGVGD Class C15 and BayesDel score 0.321305.
The variant has been reported in ClinVar with an expert panel classification of Likely Benign by the ClinGen TP53 Variant Curation Expert Panel (ClinVar ID: 184014). It has been observed in COSMIC as a somatic variant (n=14) but does not lie in a statistically significant cancer hotspot.
PVS1, PS1, PS2, PS4, PS5, PM1, PM5, PM6, PP1, PP2, PP4, PP5, BA1, BS1, BS2, BS4, BP1, BP2, BP4, BP5, BP6, and BP7 are either not met, not assessed due to lack of evidence, or not applicable per the TP53 VCEP specifications.
Tavtigian point total: PM2_Supporting (+1) + BS3_Supporting (−1) = 0 points, corresponding to a final classification of Uncertain Significance (VUS) per the TP53 VCEP v2.4.0 point-based system (VUS range: −1 to 5).
No criteria match.
Met · 3
PM2 SupportingThis variant is present at very low frequency in gnomAD v4.1 (total AF = 1.55e-05, 25/1,614,086 alleles, 0 homozygotes). The highest non-founder subpopulation frequency is South Asian at 3.29e-05 (3 alleles). All non-excluded genetic ancestry groups with multiple alleles have AF < 0.00004, and total AF < 0.00003, meeting the TP53 VCEP PM2_Supporting threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: total AF=1.55e-05 (25/1
- 614
- 086)
- max non-founder subpop AF=3.29e-05 (SAS
- 3/91
- 094)
- grpmax FAF=8.78e-06.
Sources
BS3 SupportingThe TP53 VCEP Functional-worksheet.xlsx (Supplementary Table S3) assigns BS3_Supporting to p.Thr170Met. The variant is Partially functional in the Kato et al. (PMID:12826609) assay and demonstrates no loss of function (noLOF) across all available eligible assays (Funk, Giacomelli, Kotler). This satisfies the VCEP BS3_Supporting rule: Partially functional on Kato data AND no evidence of LOF by all available assays. Details ▾Hide ▴
Evidence considered
- VCEP Functional-worksheet.xlsx: T170M = BS3_Supporting
- Kato: Partially functional
- Funk: noLOF
- Giacomelli: noLOF
- Kotler: noLOF
- Kawaguchi: NA.
Sources
vcep_functional_worksheetcspec ↗
Not met · 9 · evaluated, threshold not reached
PS1 PS1 requires the same amino acid change (p.Thr170Met) to be previously established as Pathogenic or Likely Pathogenic per the TP53 VCEP specifications. The ClinGen TP53 VCEP has classified this exact variant (NM_000546.5:c.509C>T, p.Thr170Met) as Likely Benign, and no other nucleotide change encoding p.Thr170Met has been classified as P/LP by the VCEP. Details ▾Hide ▴
PS3 The TP53 VCEP Functional-worksheet.xlsx assigns BS3_Supporting (not PS3) to p.Thr170Met. Kato assay: Partially functional; no loss of function by Funk, Giacomelli, or Kotler assays. Functional evidence supports a benign effect, contradicting PS3. Details ▾Hide ▴
Evidence considered
- VCEP Functional-worksheet.xlsx: T170M = BS3_Supporting (Kato: Partially functional
- Funk: noLOF
- Giacomelli: noLOF
- Kotler: noLOF).
Sources
vcep_functional_worksheetcspec ↗
PM1 Thr170 is not among the VCEP-specified PM1 hot-spot codons (175, 245, 248, 249, 273, 282). The alternative PM1 rule via cancerhotspots.org requires ≥10 somatic occurrences for the same amino acid change (T170M); cancerhotspots.org does not list T170M as a significant hotspot (residue_significant=false, exact_variant_listed=no). Details ▾Hide ▴
Evidence considered
- Codon 170 not in VCEP PM1 list
- cancerhotspots.org negative for T170M
- 14 COSMIC entries do not qualify under the VCEP cancerhotspots rule.
Sources
PM5 PM5 requires a different missense variant at the same amino acid residue (Thr170) previously classified as Pathogenic or Likely Pathogenic per the TP53 VCEP specifications. The pm5_candidates search returned no P/LP comparator variants at codon 170. All T170 substitutions in the VCEP functional worksheet are assigned BS3_Supporting or No evidence, none are P/LP. Details ▾Hide ▴
Evidence considered
- No P/LP comparator at codon 170
- all T170 substitutions in VCEP worksheet have BS3_Supporting or No evidence.
Sources
vcep_functional_worksheetcspec ↗
PP3 The TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2) assigns 'No evidence' to c.509C>T (p.Thr170Met). The variant is aGVGD Class C15 with BayesDel score 0.321305. Per the VCEP PP3/BP4 flowchart, Class C15 variants with BayesDel ≥0.16 would ordinarily receive PP3_Supporting, but the VCEP's pre-computed table has specifically overridden this to 'No evidence', indicating the VCEP does not consider in silico evidence sufficient for PP3 application at this residue. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.509C>T = 'No evidence'
- aGVGD Class C15
- BayesDel=0.321305.
Sources
BA1 The TP53 VCEP BA1 threshold requires a filtering allele frequency (FAF) ≥0.001 (0.1%) in a continental subpopulation. gnomAD v4.1 grpmax FAF = 8.78e-06, far below this threshold. The variant is too rare in population databases to meet BA1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF=8.78e-06
- highest subpop AF=3.29e-05 (SAS)
- both far below BA1 threshold of ≥0.001.
Sources
BS1 The TP53 VCEP BS1 threshold requires a filtering allele frequency (FAF) ≥0.0003 (0.03%) but <0.001 in a continental subpopulation. gnomAD v4.1 grpmax FAF = 8.78e-06, which is below the BS1 threshold. Even the highest raw subpopulation AF (South Asian, 3.29e-05) is below 0.0003. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: grpmax FAF=8.78e-06
- highest subpop AF=3.29e-05 (SAS
- 3/91
- 094)
- both below BS1 threshold of ≥0.0003.
Sources
BP4 The TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2) assigns 'No evidence' to c.509C>T (p.Thr170Met). Although the BayesDel score (0.321305) is elevated, the aGVGD class is C15 (not C65), and the VCEP's pre-computed table specifically assigns 'No evidence' rather than BP4, indicating the VCEP does not consider the in silico evidence sufficient for either PP3 or BP4 at this residue. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.509C>T = 'No evidence'
- aGVGD Class C15
- BayesDel=0.321305
- SpliceAI: no predicted splicing impact.
Sources
PS5 PS5 requires a different nucleotide change at codon 170 leading to the same missense change (p.Thr170Met) that has been classified as Pathogenic. The only nucleotide change resulting in p.Thr170Met is c.509C>T, which is classified as Likely Benign by the ClinGen TP53 VCEP. No alternative nucleotide substitution at this codon has been established as P/LP per VCEP. Details ▾Hide ▴
Not assessed · 6 · no assessment recorded
PS2 No de novo occurrence data for NM_000546.5:c.509C>T was identified in the available evidence sources. None of the 24 filtered publications contained variant-specific de novo reports. Details ▾Hide ▴
Still missing
- No de novo trio data identified for this variant in any curated source or publication.
PS4 No case-control enrichment data or proband counts meeting the TP53 VCEP PS4 point-based thresholds (LFS-associated cancer scores) were available for this variant. The IARC TP53 database may contain case counts but they were not retrieved in variant-specific format usable for PS4 scoring. Details ▾Hide ▴
Evidence considered
- VCEP PS4 rules require LFS cancer point scoring per proband
- no such data available.
Still missing
- IARC TP53 database case counts not retrieved
- PS4 proband-level data with LFS cancer types needed.
Sources
PP1 No co-segregation data (variant tracking through affected family members across meioses) was identified for NM_000546.5:c.509C>T in any available source. Details ▾Hide ▴
Still missing
- No segregation data identified
- family pedigrees with this variant not available.
PP4 PP4 per the TP53 VCEP requires observations of the variant with variant allele fraction (VAF) 5-35% in blood. No VAF data was available for this variant in the evidence sources. Details ▾Hide ▴
BS2 BS2 requires observation of the variant in unrelated females who have reached at least 60 years of age without cancer. No such data was available in the evidence sources for this variant. Details ▾Hide ▴
BS4 BS4 requires observation of lack of segregation in affected family members (family members with LFS-associated cancers lacking the variant). No segregation data of any kind was identified for this variant. Details ▾Hide ▴
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies to null variants (nonsense, frameshift, canonical splice sites, initiation codon, CNVs) per the TP53 VCEP PVS1 flowchart; NM_000546.5:c.509C>T is a missense variant (p.Thr170Met) and does not fall into any PVS1-eligible variant class. Details ▾Hide ▴
Evidence considered
- Missense variant
- not a null variant
- PVS1 flowchart does not apply to missense substitutions.
Sources
cspec ↗vcep_pvs1_flowchart
PM6 VCEPThe ClinGen TP53 VCEP specifications designate PM6 as Not Applicable for TP53 variant interpretation. Details ▾Hide ▴
PP2 VCEPThe ClinGen TP53 VCEP specifications designate PP2 as Not Applicable for TP53 variant interpretation. Details ▾Hide ▴
PP5 VCEPThe ClinGen TP53 VCEP specifications designate PP5 as Not Applicable, as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP1 VCEPThe ClinGen TP53 VCEP specifications designate BP1 as Not Applicable for TP53 variant interpretation. Details ▾Hide ▴
BP2 VCEPThe ClinGen TP53 VCEP specifications designate BP2 as Not Applicable for TP53 variant interpretation. Details ▾Hide ▴
BP5 VCEPThe ClinGen TP53 VCEP specifications designate BP5 as Not Applicable for TP53 variant interpretation. Details ▾Hide ▴
BP7 N/ABP7 applies to synonymous (silent) or intronic variants. NM_000546.5:c.509C>T is a missense variant (p.Thr170Met) and does not fall under BP7 per the TP53 VCEP rules. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is specific to synonymous and intronic variants.
Sources
Identifiers
- Gene
- TP53
- Transcript
- NM_000546.5
- Coding (HGVS c.)
- NM_000546.5:c.509C>T
- Protein (HGVS p.)
- NP_000537.3:p.(Thr170Met)
- GRCh38
- chr17:7675103 G>A
- GRCh37
- chr17:7578421 G>A
- ClinVar
- 652718, 184014
- COSMIC
- COSV52701457
Gene diagram
Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.5. Select a row to find it on the plot.
TP53NM_000546.5
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
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
25 / 1,614,086 alleles
AF 1.55e-05 · 0 homozygotes · FAF 8.78e-06
gnomAD v2.1
13 / 282,706 alleles
AF 4.6e-05 · 0 homozygotes · FAF 4.74e-05
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 1.5e-05 · 25 / 1,614,086 alleles · 0 hom · FAF 8.8e-06
| South Asian3 / 91,094 | 3.3e-05 |
| European (Finnish)2 / 64,030 | 3.1e-05 |
| African/African American2 / 74,924 | 2.7e-05 |
| Admixed American1 / 60,000 | 1.7e-05 |
| European (non-Finnish)17 / 1,180,056 | 1.4e-05 |
0 alternate alleles recorded in 5 other groups: Remaining individuals, Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 4.6e-05 · 13 / 282,706 alleles · 0 hom · FAF 4.7e-05
| European (non-Finnish)10 / 129,048 | 7.7e-05 |
| African/African American1 / 24,954 | 4e-05 |
| South Asian1 / 30,616 | 3.3e-05 |
| Admixed American1 / 35,434 | 2.8e-05 |
0 alternate alleles recorded in 4 other groups: Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.54886e-05; MAF= 0.00155%, 25/1614086 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.2933e-05; MAF= 0.00329%, 3/91094 alleles, homozygotes = 0); grpmax FAF= 8.78e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.59842e-05; MAF= 0.00460%, 13/282706 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.74905e-05; MAF= 0.00775%, 10/129048 alleles, homozygotes = 0); grpmax FAF= 4.74e-05.
Other predictors
- REVEL
- 0.868
- BayesDel
- 0.321
How the predictions were used
PP3 The TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2) assigns 'No evidence' to c.509C>T (p.Thr170Met). The variant is aGVGD Class C15 with BayesDel score 0.321305. Per the VCEP PP3/BP4 flowchart, Class C15 variants with BayesDel ≥0.16 would ordinarily receive PP3_Supporting, but the VCEP's pre-computed table has specifically overridden this to 'No evidence', indicating the VCEP does not consider in silico evidence sufficient for PP3 application at this residue. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.509C>T = 'No evidence'
- aGVGD Class C15
- BayesDel=0.321305.
Sources
BP4 The TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2) assigns 'No evidence' to c.509C>T (p.Thr170Met). Although the BayesDel score (0.321305) is elevated, the aGVGD class is C15 (not C65), and the VCEP's pre-computed table specifically assigns 'No evidence' rather than BP4, indicating the VCEP does not consider the in silico evidence sufficient for either PP3 or BP4 at this residue. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.509C>T = 'No evidence'
- aGVGD Class C15
- BayesDel=0.321305
- SpliceAI: no predicted splicing impact.
Sources
BP7 N/ABP7 applies to synonymous (silent) or intronic variants. NM_000546.5:c.509C>T is a missense variant (p.Thr170Met) and does not fall under BP7 per the TP53 VCEP rules. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is specific to synonymous and intronic variants.
Sources
Statement
In silico
REVEL score = 0.868. BayesDel score = 0.321305.
9 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
-
PMID 11900253 ↗Rescuing the function of mutant p53.No paper-specific finding is recorded.
-
PMID 8023157 ↗Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations.No paper-specific finding is recorded.
-
PMID 12826609 ↗Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.Kato S et al. · 2003No paper-specific finding is recorded.
-
PMID 17311302 ↗Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database.Petitjean A et al. · 2007No paper-specific finding is recorded.
-
PMID 22653678 ↗Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: a population-based survey.Magnusson S et al. · 2012No paper-specific finding is recorded.
-
PMID 23200980 ↗Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia.Kanda M et al. · 2013No paper-specific finding is recorded.
-
PMID 25741868 ↗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.No paper-specific finding is recorded.
-
PMID 28861920 ↗Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history.de Andrade KC et al. · 2017No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
25 / 1,614,086 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
5 Likely benign · 3 Uncertain significance · 1 Uncertain Significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637581
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/184014/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-7578421-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-7675103-G-A?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000546.5%3Ac.509C…
- OncoKB ↗www.oncokb.org/gene/TP53/T170M
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121504011
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.54886e-05; MAF= 0.00155%, 25/1614086 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.2933e-05; MAF= 0.00329%, 3/91094 alleles, homozygotes = 0); grpmax FAF= 8.78e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.59842e-05; MAF= 0.00460%, 13/282706 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.74905e-05; MAF= 0.00775%, 10/129048 alleles, homozygotes = 0); grpmax FAF= 4.74e-05.
ClinVar
This variant has been reported in ClinVar as Likely benign (5 clinical laboratories) and as Uncertain significance (3 clinical laboratories) and as Uncertain Significance (1 clinical laboratory) and as Likely Benign by ClinGen TP53 Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 184014)
In silico
REVEL score = 0.868. BayesDel score = 0.321305.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52701457, n = 14 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.