About TP53
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TP53 c.716A>G, p.(Asn239Ser)
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
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: 3
Benign evidence criteria: 1
Pathogenic criteria applied · 3
PS3Strong
PS3 · strong
N239S is classified as PS3 by the TP53 VCEP Functional-worksheet (Supplementary Table S3). In the Kato et al. (PMID:12826609) functional assay, N239S is non-functional. In the three other eligible VCEP assays, N239S shows loss of function: Giacomelli (PMID:30224644): LOF; Kotler (PMID:29979965): LOF; Funk (PMID:39774325): LOF. This meets the VCEP PS3_Strong criteria: non-functional on Kato data AND loss of function by the majority of other eligible assays (3/3 LOF).
PM2Supporting
PM2 · supporting
The variant is extremely rare in population databases. In gnomAD v4.1, the global allele frequency is 6.20e-7 (1 allele / 1,613,892 alleles; 0.000062%), with the only allele observed in the European (non-Finnish) subpopulation (AF = 8.48e-7; 1/1,179,928 alleles). This is well below the VCEP PM2_Supporting threshold of <0.00003 (0.003%). The variant is absent from gnomAD v2.1 and gnomAD-Canada v1.0. No homozygotes observed.
PM5Strong
PM5 · strong
At codon 239, at least three different missense variants (N239D, N239I, N239T) have been independently classified as PS3 (Pathogenic) by the TP53 VCEP Functional-worksheet. This satisfies PM5_Strong: ≥2 different missense variants at the same amino acid residue previously determined to be pathogenic per TP53 VCEP specifications.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Per the TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2), c.716A>G (p.Asn239Ser) is assigned BP4. The variant has BayesDel score 0.10537, which is <0.16 and >-0.008, with aGVGD Class C45 (not C65). SpliceAI max delta = 0.04, indicating no predicted splicing effect (<0.2). This meets the VCEP BP4_Supporting criteria: BayesDel <0.16 and >-0.008 (excluding C65) AND no predicted differences in splicing (SpliceAI <0.2).
Recorded classification: Likely pathogenic
Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PS3 strong (+4) + PM2 supporting (+1) + PM5 strong (+4) + BP4 supporting benign (-1) = 8 points, which maps to Likely Pathogenic.
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
1 / 1,613,892 alleles
gnomAD v4.1: 1 / 1,613,892 alleles. Recorded AF 6.1962e-07. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.040 maximum delta
Recorded SpliceAI maximum delta score: 0.040. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
7 reported laboratory submissions
6 Likely pathogenic · 1 Pathogenic.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Loss-of-function; curated oncogenicity label: Oncogenic.
COSMIC
Cancer Hotspots
Somatic evidence
56 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52661127, n = 56 times).
Cancer Hotspots
This variant lies 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.
27 criteria with recorded statuses: 4 met · 5 not met · 6 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
PS3_Strong is met (+4 points): N239S is non-functional in the Kato et al. functional assay and shows loss of function in all three other eligible VCEP assays (Giacomelli, Kotler, Funk), meeting the TP53 VCEP criterion for strong pathogenic functional evidence.
PM5_Strong is met (+4 points): At codon 239, three different missense variants (N239D, N239I, N239T) have been classified as pathogenic (PS3) by the TP53 VCEP, satisfying the requirement of ≥2 different pathogenic missense variants at the same residue.
PM2_Supporting is met (+1 point): The variant is extremely rare in population databases (gnomAD v4.1 AF = 6.2e-7), well below the VCEP threshold of <0.00003.
BP4_Supporting is met (-1 point): Per the VCEP PP3-BP4-codes.xlsx, c.716A>G is assigned BP4. BayesDel score 0.10537 with aGVGD Class C45 and no predicted splicing impact (SpliceAI 0.04).
Tavtigian point total: 4 (PS3) + 4 (PM5) + 1 (PM2) - 1 (BP4) = 8 points. Under the TP53 VCEP v2.4.0 point-based framework, 6-9 points corresponds to Likely Pathogenic.
The variant has been observed in ClinVar with majority classification as Likely Pathogenic (6 clinical laboratories) and Pathogenic (1 laboratory), consistent with this adjudication.
N239S has been reported as a somatic mutation in 56 tumor samples in COSMIC and is classified as Oncogenic (Loss-of-function) by OncoKB, though these somatic data are not directly used for germline criterion points under the VCEP framework.
No criteria match.
Met · 4
PS3 StrongN239S is classified as PS3 by the TP53 VCEP Functional-worksheet (Supplementary Table S3). In the Kato et al. (PMID:12826609) functional assay, N239S is non-functional. In the three other eligible VCEP assays, N239S shows loss of function: Giacomelli (PMID:30224644): LOF; Kotler (PMID:29979965): LOF; Funk (PMID:39774325): LOF. This meets the VCEP PS3_Strong criteria: non-functional on Kato data AND loss of function by the majority of other eligible assays (3/3 LOF). Details ▾Hide ▴
Evidence considered
- VCEP Functional-worksheet PS3 assignment for N239S
- Kato et al. assay: Non-functional
- Giacomelli et al. assay: LOF
- Kotler et al. assay: LOF
- Funk et al. assay: LOF
Sources
vcep_functional_worksheetPMID:12826609 ↗
PM2 SupportingThe variant is extremely rare in population databases. In gnomAD v4.1, the global allele frequency is 6.20e-7 (1 allele / 1,613,892 alleles; 0.000062%), with the only allele observed in the European (non-Finnish) subpopulation (AF = 8.48e-7; 1/1,179,928 alleles). This is well below the VCEP PM2_Supporting threshold of <0.00003 (0.003%). The variant is absent from gnomAD v2.1 and gnomAD-Canada v1.0. No homozygotes observed. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 1 allele in 1
- 613
- 892 (AF = 6.2e-7)
- gnomAD v2.1: absent
- gnomAD-Canada v1.0: absent
- No continental subpopulation with ≥2 alleles or AF ≥0.00004
Sources
PM5 StrongAt codon 239, at least three different missense variants (N239D, N239I, N239T) have been independently classified as PS3 (Pathogenic) by the TP53 VCEP Functional-worksheet. This satisfies PM5_Strong: ≥2 different missense variants at the same amino acid residue previously determined to be pathogenic per TP53 VCEP specifications. Details ▾Hide ▴
Evidence considered
- N239D: VCEP PS3
- N239I: VCEP PS3
- N239T: VCEP PS3
- Three distinct pathogenic missense changes at codon 239 per VCEP functional assignment
Sources
vcep_functional_worksheet
BP4 SupportingPer the TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2), c.716A>G (p.Asn239Ser) is assigned BP4. The variant has BayesDel score 0.10537, which is <0.16 and >-0.008, with aGVGD Class C45 (not C65). SpliceAI max delta = 0.04, indicating no predicted splicing effect (<0.2). This meets the VCEP BP4_Supporting criteria: BayesDel <0.16 and >-0.008 (excluding C65) AND no predicted differences in splicing (SpliceAI <0.2). Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.716A>G assigned BP4
- BayesDel: 0.10537
- aGVGD Class C45
- SpliceAI max delta: 0.04
Sources
Not met · 5 · evaluated, threshold not reached
PM1 Codon 239 is not among the VCEP-designated PM1 hotspot codons (175, 245, 248, 249, 273, 282). The exact variant (N239S) is not listed as a standalone entry in cancerhotspots.org with ≥10 somatic occurrences (exact_variant_listed: no), though the residue lies in a statistically significant hotspot and COSMIC reports 56 somatic occurrences for this variant. Under the VCEP PM1 rules, neither codon-based nor cancerhotspots-based thresholds are met. Details ▾Hide ▴
Evidence considered
- Codon 239 not in VCEP PM1 hotspot list
- cancerhotspots.org: exact variant not listed
- COSMIC: 56 somatic occurrences (somatic context
- not germline hotspot criteria)
Sources
PP3 Per the TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2), c.716A>G (p.Asn239Ser) is assigned BP4, not PP3. The variant has BayesDel score 0.10537 (aGVGD Class C45), which is below the 0.16 threshold for PP3_Supporting. SpliceAI max delta = 0.04, indicating no predicted splicing effect (<0.2). Per the VCEP PP3/BP4 flowchart, aGVGD Class C45 with BayesDel <0.16 and no predicted splicing effect meets BP4, not PP3. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.716A>G assigned BP4
- BayesDel: 0.10537 (Class C45)
- SpliceAI max delta: 0.04 (no predicted splice effect)
Sources
BA1 The variant is extremely rare in gnomAD v4.1 (global AF = 6.2e-7). No continental subpopulation has a filtering allele frequency (FAF) ≥0.001 (0.1%). The VCEP BA1 stand-alone benign threshold is not approached. Details ▾Hide ▴
BS1 The variant is extremely rare in gnomAD v4.1 (global AF = 6.2e-7). No continental subpopulation has an allele frequency ≥0.0003 (0.03%). The VCEP BS1 strong benign threshold is not approached. Details ▾Hide ▴
BS3 N239S is non-functional in the Kato et al. assay (PMID:12826609) and shows loss of function in all other eligible VCEP assays (Giacomelli, Kotler, Funk). The VCEP Functional-worksheet assigns PS3, not BS3. BS3 requires the variant to be functional or partially functional on Kato data with no LOF by the majority of available assays, which is contradicted by the non-functional Kato result and uniform LOF across supporting assays. Details ▾Hide ▴
Evidence considered
- VCEP Functional-worksheet: N239S = PS3
- Kato assay: Non-functional
- All eligible assays show LOF
- does not meet BS3 functional threshold
Sources
vcep_functional_worksheet
Not assessed · 6 · no assessment recorded
PS2 No de novo observation of NM_000546.6:c.716A>G (p.Asn239Ser) with confirmed paternity and maternity was identified in the literature, ClinVar, or published databases reviewed. De novo status cannot be determined from available evidence. Details ▾Hide ▴
Still missing
- No de novo reports identified
- proband trio data would be required to assess PS2.
PS4 Although the PM2_Supporting prerequisite is satisfied (variant is extremely rare in population databases), no proband-level cancer phenotype data or case-control analysis is available to calculate Li-Fraumeni syndrome cancer points under the TP53 VCEP PS4 scoring system. The variant has 56 somatic observations in COSMIC and is listed as Oncogenic in OncoKB, but these somatic data alone do not meet the VCEP PS4 proband-based point thresholds. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF = 6.2e-7 supports PM2 but PS4 requires case enrichment data
- COSMIC: 56 somatic occurrences
- OncoKB: Oncogenic (Loss-of-function)
Still missing
- No proband-level cancer phenotype data or case-control study available
- individual clinical data with LFS cancer diagnoses needed for PS4 point calculation.
Sources
PP1 No cosegregation data identified for NM_000546.6:c.716A>G. No published pedigrees or family studies reporting segregation of this variant with Li-Fraumeni syndrome or TP53-associated cancers were found. Details ▾Hide ▴
Still missing
- No cosegregation data available
- family studies with variant carriers needed for PP1 assessment.
PP4 The TP53 VCEP PP4 criterion requires variant allele fraction (VAF) data from clinical testing to distinguish constitutional from somatic/clonal hematopoiesis origin. No VAF data or clinical phenotype information is available in the evidence reviewed. Details ▾Hide ▴
Still missing
- VAF data from clinical testing needed
- at least one observation with VAF 5-35% required for PP4_Supporting.
BS2 No data available on unrelated females aged ≥60 years without cancer who carry this variant. BS2 requires a minimum of 2 such individuals from a single source, which has not been identified. Details ▾Hide ▴
Still missing
- No observations of variant carriers meeting BS2 age and cancer-free criteria from any single data source.
BS4 No evidence of lack of segregation identified. No reports of this variant in unaffected family members of Li-Fraumeni syndrome families, nor observations in healthy elderly controls, were found in the literature or databases reviewed. Details ▾Hide ▴
Still missing
- No segregation or non-segregation data
- family studies or healthy elderly control data needed.
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. The TP53 VCEP PVS1 flowchart applies only to null variants (nonsense, frameshift, canonical ±1,2 splice site, initiation codon, and exon-level deletions). NM_000546.6:c.716A>G is a missense substitution (p.Asn239Ser). Details ▾Hide ▴
Evidence considered
- Missense variant
- does not fall into any PVS1-eligible null variant bucket.
Sources
vcep_pvs1_flowchart
PS1 N/APS1 requires a different nucleotide change yielding the same amino acid change that has been previously classified as pathogenic by the TP53 VCEP. NM_000546.6:c.716A>G (p.Asn239Ser) represents a single nucleotide substitution; no alternative nucleotide change at this position yields the same amino acid change (N239S). Details ▾Hide ▴
Evidence considered
- Single nucleotide substitution to serine at codon 239
- no alternative nucleotide path to N239S exists.
Sources
PM6 VCEPSkipped per adjudication directive. PM6 is not applicable per TP53 VCEP specifications. Details ▾Hide ▴
No further detail was recorded.
PP2 VCEPPP2 is not applicable per TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴
PP5 VCEPPP5 is not for use per the TP53 VCEP v2.4.0 specifications, as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP1 VCEPBP1 is not applicable per TP53 VCEP v2.4.0 specifications. The VCEP states this rule does not apply to TP53 as truncating variants account for only a portion of disease-causing variants. Details ▾Hide ▴
BP2 VCEPBP2 is not applicable per TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴
BP3 VCEPSkipped per adjudication directive. In-frame deletion/insertion in repetitive region; not applicable to this missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP5 VCEPBP5 is not applicable per TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴
BP6 VCEPBP6 is not applicable per TP53 VCEP v2.4.0 specifications. Details ▾Hide ▴
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants. NM_000546.6:c.716A>G is a missense variant and does not qualify for BP7 assessment. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 restricted to synonymous and intronic variants.
Sources
PS5 N/APS5 is not included in the TP53 VCEP v2.4.0 criteria specification. The same-residue different-missense-change scenario is addressed in this framework by the PM5 criterion, which has VCEP-specific strength rules. Details ▾Hide ▴
Evidence considered
- TP53 VCEP v2.4.0 does not include PS5
- PM5 covers same-residue missense comparator assessment.
Sources
Identifiers
- Gene
- TP53
- Transcript
- NM_000546.6
- Coding (HGVS c.)
- NM_000546.6:c.716A>G
- Protein (HGVS p.)
- NP_000537.3:p.(Asn239Ser)
- GRCh38
- chr17:7674247 T>C
- GRCh37
- chr17:7577565 T>C
- ClinVar
- 376637, 2748594
- COSMIC
- COSV52661127
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
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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
1 / 1,613,892 alleles
AF 6.2e-07 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.2e-07 · 1 / 1,613,892 alleles · 0 hom
| European (non-Finnish)1 / 1,179,928 | 8.5e-07 |
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.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.1962e-07; MAF= 0.00006%, 1/1613892 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47509e-07; MAF= 0.00008%, 1/1179928 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.897
- BayesDel
- 0.105
How the predictions were used
BP4 SupportingPer the TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2), c.716A>G (p.Asn239Ser) is assigned BP4. The variant has BayesDel score 0.10537, which is <0.16 and >-0.008, with aGVGD Class C45 (not C65). SpliceAI max delta = 0.04, indicating no predicted splicing effect (<0.2). This meets the VCEP BP4_Supporting criteria: BayesDel <0.16 and >-0.008 (excluding C65) AND no predicted differences in splicing (SpliceAI <0.2). Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.716A>G assigned BP4
- BayesDel: 0.10537
- aGVGD Class C45
- SpliceAI max delta: 0.04
Sources
PP3 Per the TP53 VCEP PP3-BP4-codes.xlsx (Supplementary Table S2), c.716A>G (p.Asn239Ser) is assigned BP4, not PP3. The variant has BayesDel score 0.10537 (aGVGD Class C45), which is below the 0.16 threshold for PP3_Supporting. SpliceAI max delta = 0.04, indicating no predicted splicing effect (<0.2). Per the VCEP PP3/BP4 flowchart, aGVGD Class C45 with BayesDel <0.16 and no predicted splicing effect meets BP4, not PP3. Details ▾Hide ▴
Evidence considered
- VCEP PP3-BP4-codes.xlsx: c.716A>G assigned BP4
- BayesDel: 0.10537 (Class C45)
- SpliceAI max delta: 0.04 (no predicted splice effect)
Sources
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants. NM_000546.6:c.716A>G is a missense variant and does not qualify for BP7 assessment. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 restricted to synonymous and intronic variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.897. BayesDel score = 0.10537.
8 paper records listed. 1 cited in the classification.
Cited in the classification
-
PMID 22553460 ↗The gain of function of p53 mutant p53S in promoting tumorigenesis by cross-talking with H-RasV12.Jia S et al. · 2012N239S (referred to as p53S) is the primary subject of this study. The mutant lost DNA binding activity to p21 and PERP promoters by EMSA, lost transactivation of p21, cyclin G1, PUMA, and Bax in response to irradiation by real-time PCR, and did not suppress tumorigenesis. Cooperating with H-RasV12, p53S promoted tumorigenesis in xenograft assays, demonstrating gain-of-function oncogenic properties. N239S is described as a non-functional mutation in yeast and mammalian assays.→ PS3 Names this variant
Source detail
The p53 N236S (p53 N239S in human, p53S) mutation has been shown to lose wild type p53 function by yeast assay. ... Functional assays in yeast and structure-function predictions indicate that p53 N239S is a non-functional mutation.
Location Abstract; Introduction paragraphs 2-5; Results (Figures 1-4); Discussion paragraphs 1-4
Context Mouse embryonic fibroblasts (p53-/- MEFs), EMSA with in vitro translated proteins, real-time PCR, xenograft in SCID mice, Western blotting, flow cytometry
Other recorded publications
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PMID 10366100 ↗Dominant-negative p53 mutations in rheumatoid arthritis.Han Z et al. · 1999N239S was generated by site-directed mutagenesis as one of two rheumatoid arthritis-derived p53 mutants (N239S and R213*). When transfected into HS68 dermal fibroblasts together with wild-type p53, N239S exhibited dominant-negative activity by upregulating IL-6 expression, demonstrating its ability to interfere with wild-type p53 function.Names this variant
Quoted passage
Site-directed mutagenesis was used to produce 2 RA-derived mutants: asparagine→serine at codon 239 (N239S) and arginine→stop at codon 213 (R213*).
Abstract
-
PMID 10753186 ↗High frequency in esophageal cancers of p53 alterations inactivating the regulation of genes involved in cell cycle and apoptosis.Robert V et al. · 2000N239S (AAC→AGC, Asn→Ser at codon 239) was identified as a somatic mutation in one esophageal squamous cell carcinoma among 47 mutation-positive tumors analyzed by yeast functional assay. The mutation abolished transactivation of p21, bax, and PIG3 reporter systems, classifying it as a (p21-/PIG3-/bax-) complete loss-of-function mutant.Names this variant
Quoted passage
239 | AAC→AGC | Asn→Ser
Table I (tumor O90b); Results paragraph 1
-
PMID 11429705 ↗p53 mutants can often transactivate promoters containing a p21 but not Bax or PIG3 responsive elements.Campomenosi P et al. · 2001No paper-specific finding is recorded.
-
PMID 11896595 ↗Tumour p53 mutations exhibit promoter selective dominance over wild type p53.Monti P et al. · 2002No 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 16861262 ↗Inactive full-length p53 mutants lacking dominant wild-type p53 inhibition highlight loss of heterozygosity as an important aspect of p53 status in human cancers.Dearth LR et al. · 2007No 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
1 / 1,613,892 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.040
Open source ↗
ClinVar
6 Likely pathogenic · 1 Pathogenic
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/376637/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-7577565-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-7674247-T-C?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-7674247-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000546.6%3Ac.716A…
- OncoKB ↗www.oncokb.org/gene/TP53/N239S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121521969
- 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= 6.1962e-07; MAF= 0.00006%, 1/1613892 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.47509e-07; MAF= 0.00008%, 1/1179928 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely pathogenic (6 clinical laboratories) and as Pathogenic (1 clinical laboratory). (ClinVarID = 376637)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.897. BayesDel score = 0.10537.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Loss-of-function; curated oncogenicity label: Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52661127, n = 56 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.