About MYC
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MYC c.872G>C, p.(Arg291Thr)
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 Not recorded. 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: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 and gnomAD v4.1 population databases, indicating it is a rare variant.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of in silico evidence consistently predict a neutral or benign effect: REVEL score 0.106 (well below pathogenic threshold), BayesDel score -0.387599 (negative, favoring benign), and SpliceAI max delta score 0.00 (no predicted splicing impact).
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM2 supporting, BP4 supporting benign; combination = 1 supporting + 1 supporting benign, 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.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MYC, a transcription factor, is altered by chromosomal rearrangement, amplification and overexpression in a variety of cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 22 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002467.6:c.872G>C (p.Arg291Thr) is a missense variant in MYC, a proto-oncogene located on 8q24.21.
The variant is absent from gnomAD v2.1 and v4.1 population databases (PM2_supporting).
Multiple in silico predictors consistently indicate a neutral effect: REVEL 0.106, BayesDel -0.388, SpliceAI max delta 0.00 (BP4_supporting).
The variant is absent from ClinVar and has not been reported in the literature, including COSMIC; no functional, segregation, or case-control data are available.
Overall, one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met, yielding an ACMG/AMP classification of Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PM2 SupportingThis variant is absent from gnomAD v2.1 and gnomAD v4.1 population databases, indicating it is a rare variant. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes/genomes).
- Absent from gnomAD v4.1 (exomes/genomes).
Sources
BP4 SupportingMultiple lines of in silico evidence consistently predict a neutral or benign effect: REVEL score 0.106 (well below pathogenic threshold), BayesDel score -0.387599 (negative, favoring benign), and SpliceAI max delta score 0.00 (no predicted splicing impact). Details ▾Hide ▴
Evidence considered
- REVEL: 0.106 (benign).
- BayesDel: -0.387599 (benign).
- SpliceAI max delta: 0.00 (no effect).
Sources
Not met · 22 · evaluated, threshold not reached
PS1 No different pathogenic missense variant at the same amino acid position (Arg291) has been reported in ClinVar or the literature. Details ▾Hide ▴
Evidence considered
- ClinVar contains no entries for any variant at this residue.
Still missing
- No ClinVar entries at Arg291 to compare.
Sources
PS2 No de novo data are available for this variant. Details ▾Hide ▴
Evidence considered
- No de novo observation reported in any source.
Still missing
- No parental or family data available.
PS3 No variant-specific functional data are available. OncoKB reports unknown oncogenic effect with no variant-level reviewed functional evidence. No publications containing functional characterization of p.Arg291Thr or any systematic range including this residue were identified. Details ▾Hide ▴
Evidence considered
- OncoKB classification: Unknown Oncogenic Effect. No variant-specific functional studies found in the literature.
Still missing
- No functional studies of this variant exist.
Sources
PS4 No case-control or population-based studies comparing this variant in affected versus unaffected individuals are available. Details ▾Hide ▴
Evidence considered
- No case-control or association studies identified.
Still missing
- No epidemiological data available.
PM1 p.Arg291 does not lie within a statistically significant mutational hotspot per cancerhotspots.org. Although MYC contains well-characterized functional domains (bHLH at residues ~355–410, leucine zipper at ~410–439), Arg291 resides in the central linker region outside these established critical domains, and no domain-level functional characterization exists for this residue. Details ▾Hide ▴
Evidence considered
- cancerhotspots.org: no significant hotspot at this residue. Residue 291 is outside the bHLH and leucine zipper domains.
Still missing
- No residue-specific domain characterization.
PM5 No pathogenic variant at the same codon (Arg291) has been identified in ClinVar. The PM5 candidate search returned zero same-residue comparator variants. Details ▾Hide ▴
Evidence considered
- ClinVar contains no variant at codon 291. PM5 candidate harvesting found zero candidates.
Still missing
- No same-residue comparator variants in ClinVar.
Sources
clinvar ↗pm5_candidates
PM6 No de novo observation (without confirmation of paternity and maternity) has been reported for this variant. Details ▾Hide ▴
Evidence considered
- No de novo report identified.
Still missing
- No trio or parentage data available.
PP1 No cosegregation data are available for this variant. Details ▾Hide ▴
Evidence considered
- No family-based segregation analysis available.
Still missing
- No pedigrees or segregation data.
PP2 HCI prior scores are not available for MYC (gene not supported by the HCI prior database). There is insufficient evidence to establish that MYC has a low rate of benign missense variation in the germline. Details ▾Hide ▴
Evidence considered
- HCI prior data unavailable for MYC.
Still missing
- No gene-level missense constraint metric available.
PP3 Multiple in silico predictors are benign-leaning: REVEL score 0.106 (below typical pathogenic threshold of 0.5), BayesDel score -0.387599 (negative, favoring benign), and SpliceAI max delta 0.00 (no predicted splice impact). These results do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.106 (benign-leaning).
- BayesDel: -0.387599 (benign-leaning).
- SpliceAI max delta: 0.00 (no splice impact).
Sources
PP4 No patient phenotype or clinical data are available for evaluation. Details ▾Hide ▴
Evidence considered
- No phenotype data available.
Still missing
- No clinical phenotype information provided.
PP5 This variant is absent from ClinVar; no reputable source has classified it as pathogenic. Details ▾Hide ▴
BA1 The variant is absent from gnomAD v2.1 and v4.1 (allele frequency 0%), far below the 1% threshold for BA1. Details ▾Hide ▴
BS1 The variant is absent from gnomAD v2.1 and v4.1 (allele frequency 0%), far below the 0.3% threshold for BS1. Details ▾Hide ▴
BS2 No data available regarding observation of this variant in healthy adult individuals. Details ▾Hide ▴
Evidence considered
- No healthy control observation data available.
Still missing
- No observational data in healthy adults.
BS3 No well-established functional studies demonstrating a neutral or benign effect exist for this specific variant. Details ▾Hide ▴
Evidence considered
- No functional studies of any kind identified for this variant.
Still missing
- No experimental functional data available.
BS4 No segregation data are available to evaluate lack of cosegregation with disease. Details ▾Hide ▴
Evidence considered
- No family segregation data available.
Still missing
- No pedigrees or family studies.
BP1 MYC is a proto-oncogene where gain-of-function (amplification, overexpression) is the primary established disease mechanism in cancer; it is not a gene for which primarily truncating variants are known to cause disease. Details ▾Hide ▴
Evidence considered
- MYC disease mechanism is gain-of-function
- not loss-of-function via truncation.
Sources
pvs1_gene_context
BP2 No observation of this variant in trans with a known pathogenic variant has been reported. Details ▾Hide ▴
Evidence considered
- No trans-configuration data available.
Still missing
- No phasing or compound heterozygous data.
BP5 No observation of this variant in a case with an alternative molecular basis for disease has been reported. Details ▾Hide ▴
Evidence considered
- No alternative molecular basis data available.
Still missing
- No case data with alternative diagnoses.
BP6 This variant is absent from ClinVar; no reputable source has classified it as benign. Details ▾Hide ▴
PS5 No linkage analysis or statistical genetic evidence associating this variant with disease has been reported. Details ▾Hide ▴
Evidence considered
- No linkage or family-based statistical evidence identified.
Still missing
- No family studies available.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_002467.6:c.872G>C is a missense variant (p.Arg291Thr) and does not fall into any null-variant bucket (nonsense, frameshift, or canonical ±1,2 splice consensus). The generic PVS1 decision framework (PMC6185798) does not apply to this variant class. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not a predicted null variant.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PM3 N/APM3 applies to recessive disorders when the variant is detected in trans with a pathogenic variant; no phase or genotype data are available for assessment. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to in-frame deletions/insertions or stop-loss variants that change protein length; this is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP3 N/AThis is a missense variant; BP3 applies to in-frame deletions/insertions in repetitive regions. Details ▾Hide ▴
No further detail was recorded.
BP7 N/AThis is a missense variant (p.Arg291Thr), not a synonymous variant; BP7 applies only to synonymous variants without predicted splice impact. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- MYC
- Transcript
- NM_002467.6
- Coding (HGVS c.)
- NM_002467.6:c.872G>C
- Protein (HGVS p.)
- NP_002458.2:p.(Arg291Thr)
- GRCh38
- chr8:127740465 G>C
- GRCh37
- chr8:128752711 G>C
Gene diagram
Every interpreted variant in MYC, mapped onto the exon structure of NM_002467.6. Select a row to find it on the plot.
MYCNM_002467.6
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 MYC
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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
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
Other predictors
- REVEL
- 0.106
- BayesDel
- -0.388
How the predictions were used
BP4 SupportingMultiple lines of in silico evidence consistently predict a neutral or benign effect: REVEL score 0.106 (well below pathogenic threshold), BayesDel score -0.387599 (negative, favoring benign), and SpliceAI max delta score 0.00 (no predicted splicing impact). Details ▾Hide ▴
Evidence considered
- REVEL: 0.106 (benign).
- BayesDel: -0.387599 (benign).
- SpliceAI max delta: 0.00 (no effect).
Sources
PP3 Multiple in silico predictors are benign-leaning: REVEL score 0.106 (below typical pathogenic threshold of 0.5), BayesDel score -0.387599 (negative, favoring benign), and SpliceAI max delta 0.00 (no predicted splice impact). These results do not support a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.106 (benign-leaning).
- BayesDel: -0.387599 (benign-leaning).
- SpliceAI max delta: 0.00 (no splice impact).
Sources
BP7 N/AThis is a missense variant (p.Arg291Thr), not a synonymous variant; BP7 applies only to synonymous variants without predicted splice impact. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.106. BayesDel score = -0.387599.
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 ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/?term=NM_002467.6%3Ac.872G%3EC
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/8-128752711-G-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr8-127740465-G-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/8-127740465-G-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002467.6%3Ac.872G…
- OncoKB ↗www.oncokb.org/gene/MYC/R291T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MYC+c.872G%3EC
- 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
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). REVEL score = 0.106. BayesDel score = -0.387599.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MYC, a transcription factor, is altered by chromosomal rearrangement, amplification and overexpression in a variety of cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.