About MYC
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MYC c.956C>T, p.(Thr319Ile)
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
NM_002467.5:c.956C>T is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, meeting the PM2 threshold for absent/very low frequency (<0.1%) in population databases.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no deleterious impact. REVEL score is 0.079 (well below pathogenic threshold), BayesDel score is -0.588 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta = 0.00). These results are concordant in predicting a benign effect.
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.
27 criteria with recorded statuses: 2 met · 20 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_002467.5:c.956C>T (p.Thr319Ile) is a missense variant in MYC exon 3, absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (PM2_Supporting).
Multiple in silico predictors are concordant in predicting no deleterious effect: REVEL score 0.079, BayesDel score -0.588, and SpliceAI max delta 0.00 (BP4_Supporting).
The variant is absent from ClinVar with no submissions from any laboratory, and has not been reported in COSMIC or at cancerhotspots.org. No variant-specific functional studies or clinical case reports were identified in the literature.
Under the ACMG/AMP 2015 generic classification framework, the combination of one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) results in a final classification of Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PM2 SupportingNM_002467.5:c.956C>T is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, meeting the PM2 threshold for absent/very low frequency (<0.1%) in population databases. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes).
- Absent from gnomAD v4.1 (exomes).
- Absent from gnomAD-Canada v1.0 (genomes).
Sources
BP4 SupportingMultiple lines of computational evidence suggest no deleterious impact. REVEL score is 0.079 (well below pathogenic threshold), BayesDel score is -0.588 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta = 0.00). These results are concordant in predicting a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.079 (low
- benign).
- BayesDel: -0.588253 (benign).
- SpliceAI: max delta = 0.00 (no splice impact).
Sources
Not met · 20 · evaluated, threshold not reached
PS1 No alternate nucleotide change at c.956 resulting in the same amino acid change (p.Thr319) has been reported as pathogenic. No same-codon comparator variants were identified in ClinVar. Details ▾Hide ▴
Evidence considered
- ClinVar contains no entries for NM_002467.5:c.956C>T or any alternate nucleotide change at this codon. No pathogenic same-codon comparators found.
Sources
clinvar ↗pm5_candidates
PS2 No de novo occurrence data with confirmed maternity and paternity is available for this variant. Details ▾Hide ▴
Evidence considered
- No de novo reports identified in ClinVar or the literature.
PS3 No variant-specific or range-based functional data exists for NM_002467.5:c.956C>T (p.Thr319Ile). OncoKB classifies this variant as 'Unknown Oncogenic Effect' with no reviewed functional evidence. No publications report experimental characterization of this variant or a systematically characterized range encompassing residue T319. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no variant-specific functional data. Literature_pass: 0 PMIDs identified.
Still missing
- No functional studies have been performed on this variant or a systematically characterized range that includes residue T319.
Sources
PS4 No data on variant prevalence in affected individuals versus controls is available. The variant is absent from ClinVar and COSMIC, providing no case-level observations. Details ▾Hide ▴
Evidence considered
- Absent from ClinVar
- absent from COSMIC.
Still missing
- No case-control or cohort data available for this variant.
Sources
PM1 Residue Thr319 lies in the central regulatory region of MYC (residues ~144-354), not in the critical bHLH-LZ DNA-binding domain (residues ~355-439). Cancerhotspots.org does not identify this position as a statistically significant hotspot. No evidence that residue 319 constitutes a critical functional domain. Details ▾Hide ▴
Evidence considered
- Not a cancerhotspots.org significant hotspot. T319 is in the central region
- not the bHLH-LZ domain.
PM6 No de novo occurrence data (without confirmed parentage) is available for this variant. Details ▾Hide ▴
Evidence considered
- No de novo reports identified.
PP1 No co-segregation data in affected family members is available for this variant. Details ▾Hide ▴
Evidence considered
- No family studies or segregation data identified.
PP2 No HCI prior data is available for MYC (gene not supported in the HCI database). The rate of benign missense variation in MYC has not been established for PP2 application. Details ▾Hide ▴
Evidence considered
- HCI prior not found for MYC
- gene not supported.
Still missing
- MYC is not in the HCI prior database
- PP2 cannot be applied without an established z-score or constraint metric.
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.079 (well below the 0.5 threshold for pathogenicity), BayesDel score is -0.588 (negative, predicting benign), and SpliceAI predicts no splice impact (max delta score = 0.00). Computational evidence does not meet the threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.079 (low).
- BayesDel: -0.588253 (benign).
- SpliceAI: max delta = 0.00.
Sources
PP4 No patient phenotype or family history data is available to assess whether the clinical presentation is highly specific for an MYC-related disorder. Details ▾Hide ▴
Evidence considered
- No phenotype data provided.
Still missing
- No clinical phenotype or family history available.
PP5 NM_002467.5:c.956C>T is absent from ClinVar; no reputable source has reported this variant as pathogenic. No ClinVar submissions exist for this variant. Details ▾Hide ▴
BA1 NM_002467.5:c.956C>T is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. The allele frequency does not exceed the BA1 threshold of 1%. Details ▾Hide ▴
Evidence considered
- Absent from all gnomAD datasets
- AF = 0.
Sources
BS1 NM_002467.5:c.956C>T is absent from gnomAD. The allele frequency does not exceed the BS1 threshold of 0.3%. Details ▾Hide ▴
Evidence considered
- Absent from all gnomAD datasets
- AF = 0.
Sources
BS2 No data is available on healthy adult individuals carrying this variant. The variant is absent from all population databases, precluding assessment of observation in healthy controls. Details ▾Hide ▴
Evidence considered
- Variant absent from population databases
- no healthy carriers identified.
Sources
BS3 No in vitro or in vivo functional studies demonstrating no damaging effect on protein function or splicing have been performed for this variant. OncoKB reports no reviewed functional evidence. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no functional studies identified.
Still missing
- No functional studies available for this variant.
Sources
BS4 No family segregation data is available to assess lack of segregation with disease. Details ▾Hide ▴
Evidence considered
- No segregation data available.
BP2 No data on observation of this variant in trans with a known pathogenic variant in a fully penetrant dominant gene is available. Details ▾Hide ▴
Evidence considered
- No trans-phase data available.
BP5 No data is available on an alternate molecular basis for disease in a case carrying this variant. Details ▾Hide ▴
Evidence considered
- No alternate molecular basis data available.
BP6 NM_002467.5:c.956C>T is absent from ClinVar; no reputable source has reported this variant as benign. No ClinVar submissions exist for this variant. Details ▾Hide ▴
PS5 No de novo occurrence data (with or without confirmed parentage) is available for this variant. PS5 is not part of the standard ACMG/AMP 2015 criterion set and is not applicable under the generic framework; regardless, no supporting evidence exists. Details ▾Hide ▴
Evidence considered
- No de novo reports identified.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_002467.5:c.956C>T is a missense variant (p.Thr319Ile) and does not fall into the default generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants. PVS1 is not applicable to missense variants under the ClinGen SVI PVS1 decision tree (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense substitution at c.956C>T (p.Thr319Ile)
- variant_bucket='other'
- apply_generic_pvs1_framework=false.
Sources
pvs1_variant_assessmentpvs1_generic_framework ↗
PM5 N/ANo same-residue comparator variants at codon 319 with established pathogenicity were identified. The automated PM5 candidate harvesting found zero candidates, and ClinVar contains no entries for any nucleotide change at this codon. Details ▾Hide ▴
Evidence considered
- PM5 candidate search returned 0 same-residue candidates.
Sources
pm5_candidatesclinvar ↗
BP1 N/ANo well-established germline disease association has been confirmed for MYC. The papers identified in the PVS1 gene-context search mention MYC only as a downstream target or in connection with other primary disease genes (FBXW7, APC). BP1 requires a gene for which primarily truncating variants are known to cause disease; this cannot be assessed without a definitive MYC germline disease mechanism. Details ▾Hide ▴
Evidence considered
- Literature review for MYC germline disease context found no confirmed MYC-specific germline disorder. Papers identified discuss MYC as a downstream effector in FBXW7
- APC
- and other gene disorders.
Still missing
- No established MYC-specific germline disease.
Sources
pvs1_gene_context
BP3 N/AIn-frame deletions/insertions in a repetitive region without a known function — this is a missense substitution, not an in-frame indel. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not an in-frame indel.
BP7 N/ANM_002467.5:c.956C>T is a missense variant (p.Thr319Ile), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution (p.Thr319Ile)
- not synonymous.
Identifiers
- Gene
- MYC
- Transcript
- NM_002467.5
- Coding (HGVS c.)
- NM_002467.5:c.956C>T
- Protein (HGVS p.)
- NP_002458.2:p.(Thr319Ile)
- GRCh38
- chr8:127740549 C>T
- GRCh37
- chr8:128752795 C>T
Gene diagram
Every interpreted variant in MYC, mapped onto the exon structure of NM_002467.5. Select a row to find it on the plot.
MYCNM_002467.5
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 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
- 0.079
- BayesDel
- -0.588
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no deleterious impact. REVEL score is 0.079 (well below pathogenic threshold), BayesDel score is -0.588 (negative, predicting benign), and SpliceAI predicts no splicing impact (max delta = 0.00). These results are concordant in predicting a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.079 (low
- benign).
- BayesDel: -0.588253 (benign).
- SpliceAI: max delta = 0.00 (no splice impact).
Sources
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.079 (well below the 0.5 threshold for pathogenicity), BayesDel score is -0.588 (negative, predicting benign), and SpliceAI predicts no splice impact (max delta score = 0.00). Computational evidence does not meet the threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.079 (low).
- BayesDel: -0.588253 (benign).
- SpliceAI: max delta = 0.00.
Sources
BP7 N/ANM_002467.5:c.956C>T is a missense variant (p.Thr319Ile), not a synonymous variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense substitution (p.Thr319Ile)
- not synonymous.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.079. BayesDel score = -0.588253.
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_002467.5%3Ac.956C%3ET
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/8-128752795-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr8-127740549-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/8-127740549-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002467.5%3Ac.956C…
- OncoKB ↗www.oncokb.org/gene/MYC/T319I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MYC+c.956C%3ET
- 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 = 0.079. BayesDel score = -0.588253.
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.