About MYC
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MYC c.1085C>T, p.(Ser362Phe)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign 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 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: 0
Benign evidence criteria: 4
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 4
BS1Strong
BS1 · strong
The allele frequency in the South Asian population (grpmax FAF 0.977% in gnomAD v4.1, 0.904% in v2.1) exceeds the non-VCEP BS1 threshold of >0.3%, indicating the variant is too common to be a fully penetrant pathogenic allele for a rare Mendelian disorder.
BS2Strong
BS2 · strong
This variant has been observed in 17 homozygous individuals in gnomAD v4.1 and 3 homozygous individuals in v2.1. Homozygosity at this frequency is incompatible with a fully penetrant early-onset dominant Mendelian disorder.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.445 (below the 0.5 damaging threshold), BayesDel is −0.151 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.00).
BP6Supporting
BP6 · supporting
ClinVar reports this variant as Likely benign by 2 clinical laboratories (Labcorp Genetics/Invitae and King Faisal Specialist Hospital) and Benign by 1 laboratory (Breakthrough Genomics), all with criteria provided. The aggregate classification is Likely benign (Variation ID 719682).
Recorded classification: Benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS1 strong, BS2 strong, BP4 supporting, BP6 supporting; combination = 2 strong benign + 2 supporting benign, which maps to Benign.
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
1,599 / 1,614,078 alleles
gnomAD v4.1: 1,599 / 1,614,078 alleles. Recorded AF 0.000990658. Recorded homozygote count 17.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00151455; MAF= 0.15146%, 428/282592 alleles, homozygotes = 3) and has highest observed frequency in the South Asian population (AF= 0.00996211; MAF= 0.99621%, 305/30616 alleles, homozygotes = 3); grpmax FAF= 0.00904243.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0013572204125950054, 25/18420 alleles, homozygotes = 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
3 reported laboratory submissions
2 Likely benign · 1 Benign.
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
4 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV99420567, n = 4 times).
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.
26 criteria with recorded statuses: 4 met · 13 not met · 0 not assessed · 9 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.1085C>T (p.Ser362Phe) is present at a grpmax filtering allele frequency of 0.977% in the South Asian population of gnomAD v4.1, exceeding the BS1 threshold of >0.3%, which indicates the variant is too common to be a fully penetrant pathogenic allele for a rare Mendelian disorder.
This variant has been observed in 17 homozygous individuals in gnomAD v4.1, which is incompatible with a fully penetrant early-onset dominant disorder, meeting BS2 at strong benign strength.
Multiple computational predictors indicate a benign effect: REVEL score 0.445 (below 0.5 threshold), BayesDel −0.151 (benign-leaning), and SpliceAI max delta 0.00 (no predicted splicing impact), supporting BP4.
ClinVar reports this variant as Likely benign by two clinical laboratories and Benign by one clinical laboratory (Variation ID 719682), with criteria provided, supporting BP6.
No criteria match.
Met · 4
BS1 StrongThe allele frequency in the South Asian population (grpmax FAF 0.977% in gnomAD v4.1, 0.904% in v2.1) exceeds the non-VCEP BS1 threshold of >0.3%, indicating the variant is too common to be a fully penetrant pathogenic allele for a rare Mendelian disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 SAS: AF=0.996%
- 305/30616 alleles
- 3 homozygotes
- grpmax FAF=0.904%
- gnomAD v4.1 SAS: AF=1.032%
- 940/91072 alleles
- 14 homozygotes
- grpmax FAF=0.977%
Sources
BS2 StrongThis variant has been observed in 17 homozygous individuals in gnomAD v4.1 and 3 homozygous individuals in v2.1. Homozygosity at this frequency is incompatible with a fully penetrant early-onset dominant Mendelian disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 3 homozygotes (428 heterozygotes)
- gnomAD v4.1: 17 homozygotes (1599 heterozygotes)
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.445 (below the 0.5 damaging threshold), BayesDel is −0.151 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.00). Details ▾Hide ▴
Evidence considered
- REVEL: 0.445 (below 0.5 damaging threshold)
- BayesDel: -0.151 (benign-leaning prediction)
- SpliceAI: max delta 0.00 (no predicted splicing alteration)
Sources
BP6 SupportingClinVar reports this variant as Likely benign by 2 clinical laboratories (Labcorp Genetics/Invitae and King Faisal Specialist Hospital) and Benign by 1 laboratory (Breakthrough Genomics), all with criteria provided. The aggregate classification is Likely benign (Variation ID 719682). Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 719682: Likely benign (2 clinical labs
- criteria provided)
- Benign (1 lab
- review status: criteria provided
- single submitter.
Sources
Not met · 13 · evaluated, threshold not reached
PS3 No well-established in vitro or in vivo functional studies support a damaging effect on MYC. OncoKB classifies this variant as 'Unknown Oncogenic Effect' with no variant-specific functional evidence. No publications with functional data for p.Ser362Phe were identified. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no variant-specific reviewed functional evidence.
Still missing
- No functional studies of p.Ser362Phe were found.
Sources
PS4 No case-control or cohort studies demonstrate enrichment of this variant in affected individuals. ClinVar contains only benign/likely benign classifications. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 719682: Likely benign (2 labs)
- Benign (1 lab)
- no pathogenic submissions.
Still missing
- No affected-case enrichment data available.
Sources
PM1 This variant does not lie in a statistically significant mutational hotspot or well-established critical functional domain. The hotspot analysis found residue_significant=false. Details ▾Hide ▴
Evidence considered
- Hotspot analysis: residue not significant
- exact variant not listed in curated hotspot catalog.
PM2 This variant is present in gnomAD population databases at frequencies above the PM2 threshold of <0.1% (v2.1 overall AF=0.151%; v4.1 overall AF=0.099%). The presence of 17 homozygous individuals in v4.1 further argues against rarity. PM2 is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 428/282592 alleles
- AF=0.151%
- 3 homozygotes
- gnomAD v4.1: 1599/1614078 alleles
- AF=0.099%
- 17 homozygotes
Sources
PP1 No segregation data are available for this variant. No family studies with cosegregation analysis were identified. Details ▾Hide ▴
Still missing
- No segregation or family studies found.
PP2 MYC is not an established gene with a low rate of benign missense variation for which missense variants are a common mechanism of germline disease. MYC is primarily known as a somatic oncogene; its germline disease association is tenuous. Details ▾Hide ▴
Evidence considered
- pvs1_gene_context identifies minimal germline disease evidence for MYC
- no constraint data supporting low benign missense rate.
Sources
pvs1_gene_context
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.445 (below the 0.5 damaging threshold), BayesDel is −0.151 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.00). Details ▾Hide ▴
Evidence considered
- REVEL: 0.445 (below 0.5 damaging threshold)
- BayesDel: -0.151 (benign-leaning)
- SpliceAI: max delta 0.00 (no predicted splicing impact)
Sources
PP4 No patient phenotype or clinical data specific to this variant are available. No case reports describing individuals harboring this variant with a consistent phenotype were identified. Details ▾Hide ▴
Still missing
- No phenotype data available for variant carriers.
PP5 ClinVar reports this variant as Likely benign (2 clinical laboratories) and Benign (1 clinical laboratory). No reputable source reports it as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar Variation ID 719682: Likely benign and Benign classifications only
- no pathogenic reports.
Sources
BA1 The highest population frequency (grpmax FAF) is 0.977% in gnomAD v4.1 (South Asian), which is below the non-VCEP BA1 threshold of >1%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF (SAS): 0.904%
- gnomAD v4.1 grpmax FAF (SAS): 0.977%
Sources
BS3 No well-established in vitro or in vivo functional studies demonstrate no damaging effect on MYC protein function for p.Ser362Phe. No variant-specific functional studies were identified. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no variant-specific benign functional evidence.
Still missing
- No functional studies of p.Ser362Phe were identified.
Sources
BS4 No segregation data demonstrating lack of cosegregation with disease are available for this variant. Details ▾Hide ▴
Still missing
- No segregation or family studies identified.
BP1 MYC is primarily known as a somatic oncogene, not a gene where primarily truncating variants cause a specific Mendelian germline disorder. The germline disease context is limited and does not establish missense variants as secondary to a predominantly truncating mechanism. Details ▾Hide ▴
Evidence considered
- pvs1_gene_context: limited germline disease support
- no established truncation-predominant disease mechanism for MYC.
Sources
pvs1_gene_context
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_002467.6:c.1085C>T is a missense variant (p.Ser362Phe), not a null variant (nonsense, frameshift, or canonical splice ±1,2). The generic PVS1 framework per PMC6185798 does not apply. Details ▾Hide ▴
Evidence considered
- Missense substitution in exon 3
- variant_bucket='other'
- apply_generic_pvs1_framework=false.
Sources
pvs1_variant_assessment
PS1 N/ANo known pathogenic missense variant at residue Ser362 has been established. No comparator pathogenic variant with the same amino acid change from a different nucleotide change was identified. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json reports found=false
- no same-residue pathogenic comparators available.
Sources
pm5_candidates
PS2 N/ANo de novo data available for this variant; no trio or parentage studies were identified. Details ▾Hide ▴
No further detail was recorded.
PM5 N/ANo pathogenic missense variant at the same residue (Ser362) with a different amino acid change was identified in ClinVar. The pm5 candidate search returned no same-residue comparator variants. Details ▾Hide ▴
Evidence considered
- pm5_candidates: found=false
- no same-residue pathogenic comparators in ClinVar.
Sources
pm5_candidates
PM6 N/ANo de novo observations have been reported for this variant. Details ▾Hide ▴
No further detail was recorded.
BP2 N/ANo data on trans or cis configurations with known pathogenic variants are available. Details ▾Hide ▴
No further detail was recorded.
BP5 N/ANo case data identifying an alternate molecular basis for disease in a proband carrying this variant are available. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_002467.6:c.1085C>T is a missense variant (p.Ser362Phe), not a synonymous variant. BP7 applies only to silent/synonymous variants. Details ▾Hide ▴
No further detail was recorded.
PS5 N/ANo de novo reports exist for this variant; PS5 requires a de novo observation with confirmed maternity/paternity but without full parental confirmation. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- MYC
- Transcript
- NM_002467.6
- Coding (HGVS c.)
- NM_002467.6:c.1085C>T
- Protein (HGVS p.)
- NP_002458.2:p.(Ser362Phe)
- GRCh38
- chr8:127740678 C>T
- GRCh37
- chr8:128752924 C>T
- ClinVar
- 719682
- COSMIC
- COSV99420567
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
1,599 / 1,614,078 alleles
AF 0.000991 · 17 homozygotes · FAF 0.00977
gnomAD v2.1
428 / 282,592 alleles
AF 0.00151 · 3 homozygotes · FAF 0.00904
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00099 · 1599 / 1,614,078 alleles · 17 hom · FAF 0.0098
| South Asian940 / 91,072 | 0.0114 hom |
| Middle Eastern52 / 6,062 | 0.00862 hom |
| Remaining individuals78 / 62,510 | 0.0012 |
| Admixed American40 / 60,014 | 0.00067 |
| European (non-Finnish)485 / 1,180,024 | 0.000411 hom |
| African/African American4 / 74,994 | 5.3e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, East Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.0015 · 428 / 282,592 alleles · 3 hom · FAF 0.009
| South Asian305 / 30,616 | 0.013 hom |
| Remaining individuals15 / 7,222 | 0.0021 |
| Admixed American25 / 35,432 | 0.00071 |
| European (non-Finnish)83 / 128,956 | 0.00064 |
0 alternate alleles recorded in 4 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish).
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000990658; MAF= 0.09907%, 1599/1614078 alleles, homozygotes = 17) and has highest observed frequency in the South Asian population (AF= 0.0103215; MAF= 1.03215%, 940/91072 alleles, homozygotes = 14); grpmax FAF= 0.00977366.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00151455; MAF= 0.15146%, 428/282592 alleles, homozygotes = 3) and has highest observed frequency in the South Asian population (AF= 0.00996211; MAF= 0.99621%, 305/30616 alleles, homozygotes = 3); grpmax FAF= 0.00904243.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0013572204125950054, 25/18420 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.445
- BayesDel
- -0.151
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. REVEL score is 0.445 (below the 0.5 damaging threshold), BayesDel is −0.151 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.00). Details ▾Hide ▴
Evidence considered
- REVEL: 0.445 (below 0.5 damaging threshold)
- BayesDel: -0.151 (benign-leaning prediction)
- SpliceAI: max delta 0.00 (no predicted splicing alteration)
Sources
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.445 (below the 0.5 damaging threshold), BayesDel is −0.151 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.00). Details ▾Hide ▴
Evidence considered
- REVEL: 0.445 (below 0.5 damaging threshold)
- BayesDel: -0.151 (benign-leaning)
- SpliceAI: max delta 0.00 (no predicted splicing impact)
Sources
BP7 N/ANM_002467.6:c.1085C>T is a missense variant (p.Ser362Phe), not a synonymous variant. BP7 applies only to silent/synonymous variants. 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 = 0.445. BayesDel score = -0.151424.
2 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
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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.Richards S et al. · 2015Standards 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. This is a methodological framework paper describing the ACMG/AMP 2015 variant classification criteria.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. This is a methodological framework paper that refines the ACMG/AMP classification system.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1,599 / 1,614,078 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
2 Likely benign · 1 Benign
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/variation/719682/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/8-128752924-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr8-127740678-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/8-127740678-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002467.6%3Ac.1085…
- OncoKB ↗www.oncokb.org/gene/MYC/S362F
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=214699481
- 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= 0.000990658; MAF= 0.09907%, 1599/1614078 alleles, homozygotes = 17) and has highest observed frequency in the South Asian population (AF= 0.0103215; MAF= 1.03215%, 940/91072 alleles, homozygotes = 14); grpmax FAF= 0.00977366.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00151455; MAF= 0.15146%, 428/282592 alleles, homozygotes = 3) and has highest observed frequency in the South Asian population (AF= 0.00996211; MAF= 0.99621%, 305/30616 alleles, homozygotes = 3); grpmax FAF= 0.00904243.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0013572204125950054, 25/18420 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 719682)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.445. BayesDel score = -0.151424.
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 previously been reported in somatic cancers (COSMIC; COSV99420567, n = 4 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.