About RICTOR
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
RICTOR c.3667G>T, p.(Asp1223Tyr)
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: 0
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_152756.4:c.3667G>T is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), consistent with a rare variant absent from general population controls.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
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; combination = 1 supporting, 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
0.050 maximum delta
Recorded SpliceAI maximum delta score: 0.050. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
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. RICTOR, a core component of the oncogenic mTOR2 complex, is altered by amplification or mutation in various 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: 1 met · 9 not met · 10 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_152756.4:c.3667G>T (p.Asp1223Tyr) is a missense variant in RICTOR. It is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (PM2_Supporting).
This variant is absent from ClinVar; no reputable source has classified it as pathogenic or benign. It is absent from COSMIC and does not lie in a statistically significant mutational hotspot.
Computational predictors are equivocal: REVEL score is 0.471 (intermediate, below the typical 0.5 pathogenicity threshold), BayesDel is 0.102, and SpliceAI predicts no significant splice impact (max delta 0.05). These do not meet PP3 or BP4 thresholds.
No variant-specific functional studies, segregation data, de novo reports, or case-control data are available. OncoKB reports Unknown Oncogenic Effect.
Only one criterion is met: PM2 (supporting). Under the generic ACMG/AMP 2015 classification framework (PMID:25741868), a single supporting criterion is insufficient to classify this variant as likely pathogenic or likely benign. This variant is classified as a Variant of Uncertain Significance (VUS).
No criteria match.
Met · 1
PM2 SupportingNM_152756.4:c.3667G>T is absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), consistent with a rare variant absent from general population controls. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (AC=null
- AN=null).
- Absent from gnomAD v4.1 (AC=null
- Absent from gnomAD-Canada v1.0 (AC=0).
Sources
Not met · 9 · evaluated, threshold not reached
PS3 No well-established functional studies demonstrating a damaging effect have been identified for this variant. OncoKB reports 'Unknown Oncogenic Effect' with no variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no variant-specific functional studies found.
Still missing
- No in vitro or in vivo functional data available for p.Asp1223Tyr.
Sources
PM1 This variant does not lie in a statistically significant mutational hotspot per CancerHotspots.org, nor in a well-established functional domain without benign variation. Details ▾Hide ▴
Evidence considered
- CancerHotspots.org: residue Asp1223 not a significant hotspot
- exact variant not listed.
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.471 (below the typical pathogenic threshold of 0.5 for supporting evidence). BayesDel score is 0.102. SpliceAI predicts no significant splice impact (max delta score 0.05). Details ▾Hide ▴
Evidence considered
- REVEL: 0.471 (intermediate
- below typical 0.5 pathogenicity threshold).
- BayesDel: 0.102 (low).
- SpliceAI: max delta 0.05 (no predicted splice impact).
Sources
PP5 NM_152756.4:c.3667G>T is absent from ClinVar; no reputable source has reported this variant as pathogenic. OncoKB classifies this variant as 'Unknown Oncogenic Effect.' Details ▾Hide ▴
BA1 NM_152756.4:c.3667G>T is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. The allele frequency is 0, which does not meet the BA1 threshold (>1% for non-VCEP generic ACMG). Details ▾Hide ▴
Evidence considered
- Allele frequency = 0 in all population databases
- does not meet BA1 threshold.
Sources
BS1 NM_152756.4:c.3667G>T is absent from gnomAD. The allele frequency is 0, which does not meet the BS1 threshold (>0.3% for non-VCEP generic ACMG). Details ▾Hide ▴
Evidence considered
- Allele frequency = 0 in all population databases
- does not meet BS1 threshold.
Sources
BP1 Although literature suggests RICTOR loss of function may contribute to germline disease, the gene-disease relationship is preliminary (literature_only, no established inheritance pattern). Truncating variants have not been definitively established as the primary disease mechanism for RICTOR. BP1 cannot be applied. Details ▾Hide ▴
Evidence considered
- RICTOR germline disease context found but preliminary
- no established disease mechanism confirming primarily truncating variants cause disease.
Still missing
- RICTOR germline disease association requires further validation before BP1 can be applied.
Sources
pvs1_gene_context
BP4 Multiple lines of computational evidence do not consistently predict no impact on the gene product. REVEL score is 0.471 (intermediate, not clearly benign), BayesDel is 0.102 (low but not definitively benign), and SpliceAI predicts no splice impact. The evidence is mixed and does not meet the threshold for BP4. Details ▾Hide ▴
Evidence considered
- REVEL: 0.471 (intermediate
- not clearly benign).
- BayesDel: 0.102 (low).
- SpliceAI: max delta 0.05 (no splice impact).
Sources
BP6 No reputable source has reported NM_152756.4:c.3667G>T as benign. The variant is absent from ClinVar. Details ▾Hide ▴
Evidence considered
- ClinVar: no entries
- no reputable source classification as benign.
Sources
Not assessed · 10 · no assessment recorded
PS2 No de novo data (with or without confirmed parentage) are available for NM_152756.4:c.3667G>T. Details ▾Hide ▴
Still missing
- No trio or de novo sequencing data available for this variant.
PS4 No case-control or prevalence data comparing affected individuals to controls are available for this variant. Details ▾Hide ▴
Still missing
- No case-control studies or prevalence data in affected populations.
PM6 No de novo data (with or without confirmed parentage) are available for NM_152756.4:c.3667G>T. Details ▾Hide ▴
Still missing
- No de novo sequencing data available.
PP1 No co-segregation data are available for this variant; no family studies have reported NM_152756.4:c.3667G>T. Details ▾Hide ▴
Still missing
- No family segregation data available.
PP2 HCI prior probability data are not available for RICTOR; cannot assess whether the gene has a low rate of benign missense variation relative to pathogenic missense variation. Details ▾Hide ▴
Evidence considered
- HCI prior: not found for RICTOR.
Still missing
- No HCI prior or gene-level missense constraint data for RICTOR.
PP4 No patient phenotype data are available to assess whether the clinical presentation is highly specific for a RICTOR-associated disease. Details ▾Hide ▴
Still missing
- No patient phenotype information provided.
BS2 No data are available on observation of this variant in healthy adults for a disorder expected to be fully penetrant. Details ▾Hide ▴
Still missing
- No healthy adult observation data available.
BS3 No well-established functional studies demonstrating no deleterious effect are available for this variant. Details ▾Hide ▴
Still missing
- No functional studies (benign or pathogenic) available for p.Asp1223Tyr.
BS4 No segregation data are available to assess lack of co-segregation with disease. Details ▾Hide ▴
Still missing
- No family segregation data available.
BP5 No data are available on an alternate molecular basis for disease in a case harboring this variant. Details ▾Hide ▴
Still missing
- No alternate molecular basis data available.
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_152756.4:c.3667G>T is a missense substitution (p.Asp1223Tyr). It does not fall into the null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice variants) required for generic PVS1 application per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
- Variant is missense
- variant_bucket='other'
- apply_generic_pvs1_framework=false.
Sources
PS1 N/ANo known pathogenic variant with the same amino acid change (p.Asp1223Tyr) has been identified in ClinVar or the literature. No comparator exists for PS1 assessment. Details ▾Hide ▴
Evidence considered
- ClinVar contains no entries for this variant or for any other pathogenic variant at Asp1223.
Sources
PM3 N/APM3 requires observation of the variant in trans with a pathogenic variant for recessive disorders. RICTOR has no established recessive disease association, and no phase data are available. Details ▾Hide ▴
Evidence considered
- No recessive disease association established for RICTOR
- no phase data.
PM4 N/APM4 applies to protein length changes due to in-frame deletions/insertions or stop-loss variants. NM_152756.4:c.3667G>T is a missense substitution. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- PM4 applies only to protein length-altering variants.
PM5 N/ANo pathogenic missense variants have been identified at the same amino acid residue (Asp1223) in ClinVar. PM5 candidate harvesting returned zero candidates at this residue. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: 0 same-residue candidate variants at Asp1223.
Sources
pm5_candidatesclinvar ↗
BP2 N/ANo observation of this variant in trans with a pathogenic variant. BP2 requires observation in trans with a known pathogenic dominant variant or for recessive disorders; neither condition is established for RICTOR. Details ▾Hide ▴
No further detail was recorded.
BP3 N/AIn-frame deletions/insertions in repetitive regions without known function. NM_152756.4:c.3667G>T is a missense substitution, not an in-frame indel. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- BP3 applies only to in-frame indels.
BP7 N/ANM_152756.4:c.3667G>T is a missense variant (p.Asp1223Tyr), not a synonymous variant. BP7 applies only to synonymous variants without predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- BP7 applies only to synonymous variants.
PS5 N/ANo established pathogenic missense variant at the same amino acid residue (Asp1223) has been identified to serve as a comparator. PM5 candidate search returned zero candidates. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: 0 same-residue candidates
- no comparator missense variant at Asp1223.
Sources
pm5_candidates
Identifiers
- Gene
- RICTOR
- Transcript
- NM_152756.4
- Coding (HGVS c.)
- NM_152756.4:c.3667G>T
- Protein (HGVS p.)
- NP_689969.2:p.(Asp1223Tyr)
- GRCh38
- chr5:38950181 C>A
- GRCh37
- chr5:38950283 C>A
Gene diagram
Every interpreted variant in RICTOR, mapped onto the exon structure of NM_152756.4. Select a row to find it on the plot.
RICTORNM_152756.4
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 RICTOR
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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
- 0.471
- BayesDel
- 0.102
How the predictions were used
PP3 Multiple in silico predictors do not support a deleterious effect. REVEL score is 0.471 (below the typical pathogenic threshold of 0.5 for supporting evidence). BayesDel score is 0.102. SpliceAI predicts no significant splice impact (max delta score 0.05). Details ▾Hide ▴
Evidence considered
- REVEL: 0.471 (intermediate
- below typical 0.5 pathogenicity threshold).
- BayesDel: 0.102 (low).
- SpliceAI: max delta 0.05 (no predicted splice impact).
Sources
BP4 Multiple lines of computational evidence do not consistently predict no impact on the gene product. REVEL score is 0.471 (intermediate, not clearly benign), BayesDel is 0.102 (low but not definitively benign), and SpliceAI predicts no splice impact. The evidence is mixed and does not meet the threshold for BP4. Details ▾Hide ▴
Evidence considered
- REVEL: 0.471 (intermediate
- not clearly benign).
- BayesDel: 0.102 (low).
- SpliceAI: max delta 0.05 (no splice impact).
Sources
BP7 N/ANM_152756.4:c.3667G>T is a missense variant (p.Asp1223Tyr), not a synonymous variant. BP7 applies only to synonymous variants without predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- BP7 applies only to synonymous variants.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.471. BayesDel score = 0.102236.
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 0.050
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_152756.4%3Ac.3667G%3ET
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/5-38950283-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr5-38950181-C-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/5-38950181-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_152756.4%3Ac.3667…
- OncoKB ↗www.oncokb.org/gene/RICTOR/D1223Y
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=RICTOR+c.3667G%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 = 0.05). REVEL score = 0.471. BayesDel score = 0.102236.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. RICTOR, a core component of the oncogenic mTOR2 complex, is altered by amplification or mutation in various 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.