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EIF1AXc.26G>AUncertain significance
Print report
Variant interpretation report

EIF1AX c.26G>A, p.(Gly9Asp)

NM_001412.4:c.26G>A NP_001403.1:p.(Gly9Asp) View identifiers
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.

About EIF1AX

No gene-level summary was recorded for this case.

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: 3 Benign evidence criteria: 1
Pathogenic criteria applied · 3
PS3Supporting
PS3 · supporting

Functional characterization of the EIF1AX N-terminal tail (NTT) domain, where p.Gly9Asp resides, was performed by Sehrawat et al. (PMID:30420357). The G9D/R13H double mutant showed reduced binding to ribosomal protein Rps10 in vitro, consistent with impaired scanning arrest and gain-of-function. Additionally, G9R (same position, different substitution) and other NTT mutants (G6D, G8R, K10E) showed enhanced translation of long 5'UTR mRNAs. The exact G9D single mutant was generated but its standalone functional data were not separately reported; the G9D/R13H double mutant data and same-position G9R data are suggestive but not definitive for the isolated G9D variant. The somatic OncoKB curation classifies this variant as Likely Oncogenic with Likely Gain-of-function effect, providing additional orthogonal support.

PM1Moderate
PM1 · moderate

The variant p.Gly9Asp is located in the N-terminal tail (NTT) of EIF1AX (residues ~2-15), a well-characterized functional domain critical for translation initiation fidelity. The NTT is established as a hotspot for cancer-associated somatic mutations in uveal melanoma, thyroid cancer, and ovarian cancer (PMID:30420357, PMID:30305285). Cancerhotspots.org identifies this residue as statistically significant. Multiple publications confirm that NTT mutations confer gain-of-function by impairing scanning arrest and enhancing translation of cell cycle genes. Gly9 is among the most frequently mutated residues in the NTT domain.

PM2Supporting
PM2 · supporting

This variant is absent from large population databases. gnomAD v2.1: absent. gnomAD v4.1: 0 alleles out of 1,168,429 (AF = 0.0%). gnomAD-Canada v1.0: absent. The variant meets the PM2 threshold of <0.1% allele frequency in all populations.

Benign criteria applied · 1
BP4Supporting
BP4 · supporting

Multiple lines of computational evidence suggest no impact on the gene product. BayesDel score is -0.034 (negative scores predict a benign effect). SpliceAI max delta score is 0.02, predicting no splicing impact. REVEL and HCI prior are unavailable but the available in silico tools consistently support a neutral or benign prediction.

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: PS3 supporting, PM1 moderate, PM2 supporting, BP4 supporting benign; combination = 1 moderate + 2 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.

SpliceAI score
0.020 maximum delta

Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded. ClinVar API review status: criteria provided, single submitter.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.

Applied · PS3 → OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
6 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV63309275, n = 6 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

29 criteria with recorded statuses: 4 met · 6 not met · 13 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_001412.4:c.26G>A (p.Gly9Asp) is a missense variant in exon 2 of EIF1AX, a gene encoding a translation initiation factor in which N-terminal tail (NTT) missense mutations are established oncogenic drivers.

The variant is absent from gnomAD v2.1 and v4.1 (0/1,168,429 alleles), meeting PM2 (supporting).

The p.Gly9 residue lies within the NTT functional domain (residues ~2-15), a well-characterized hotspot for gain-of-function cancer mutations that impair scanning arrest and enhance translation of cell cycle genes. This satisfies PM1 at moderate strength.

Functional characterization by Sehrawat et al. (2019) demonstrated that the G9D/R13H double mutant reduces binding to ribosomal protein Rps10, and other NTT mutants including G9R (same position) enhance translation of long 5'UTR mRNAs. OncoKB independently curates this variant as Likely Oncogenic with Likely Gain-of-function effect. This satisfies PS3 at supporting strength.

In silico predictors favor a neutral effect: BayesDel score is -0.034 (predicted benign) and SpliceAI max delta is 0.02 (no splice impact). This satisfies BP4 (supporting benign).

The overall evidence profile consists of one moderate pathogenic criterion (PM1), two supporting pathogenic criteria (PM2, PS3), and one supporting benign criterion (BP4). Per the generic ACMG/AMP 2015 combination rules (PMID:25741868), one moderate plus two supporting criteria does not reach the threshold for Likely Pathogenic (which requires two moderate and two supporting, or three moderate, or one strong and two supporting). The single supporting benign criterion does not independently reach any benign classification threshold. The variant is therefore classified as a Variant of Uncertain Significance (VUS).

Met · 4

PS3 SupportingFunctional characterization of the EIF1AX N-terminal tail (NTT) domain, where p.Gly9Asp resides, was performed by Sehrawat et al. (PMID:30420357). The G9D/R13H double mutant showed reduced binding to ribosomal protein Rps10 in vitro, consistent with impaired scanning arrest and gain-of-function. Additionally, G9R (same position, different substitution) and other NTT mutants (G6D, G8R, K10E) showed enhanced translation of long 5'UTR mRNAs. The exact G9D single mutant was generated but its standalone functional data were not separately reported; the G9D/R13H double mutant data and same-position G9R data are suggestive but not definitive for the isolated G9D variant. The somatic OncoKB curation classifies this variant as Likely Oncogenic with Likely Gain-of-function effect, providing additional orthogonal support. Details ▾Hide ▴
Evidence considered
  • G9D/R13H double mutant exhibited reduced Rps10 binding in in vitro pull-down assay (PMID:30420357
  • Figure 8)
  • G9R single mutant (same residue) and other NTT mutants showed enhanced scanning of long 5'UTR mRNAs (PMID:30420357
  • Figure 7)
  • OncoKB curates p.G9D as Likely Oncogenic
  • Likely Gain-of-function
Still missing
  • G9D single mutant functional data not separately reported
  • primary evidence is from G9D/R13H double mutant and same-residue G9R.
Sources
PMID:30420357 ↗oncokb ↗
PM1 ModerateThe variant p.Gly9Asp is located in the N-terminal tail (NTT) of EIF1AX (residues ~2-15), a well-characterized functional domain critical for translation initiation fidelity. The NTT is established as a hotspot for cancer-associated somatic mutations in uveal melanoma, thyroid cancer, and ovarian cancer (PMID:30420357, PMID:30305285). Cancerhotspots.org identifies this residue as statistically significant. Multiple publications confirm that NTT mutations confer gain-of-function by impairing scanning arrest and enhancing translation of cell cycle genes. Gly9 is among the most frequently mutated residues in the NTT domain. Details ▾Hide ▴
Evidence considered
  • NTT domain (residues 2-15) is a critical functional domain for translation initiation and scanning arrest
  • Cancerhotspots.org identifies p.Gly9 as a statistically significant hotspot residue
  • Multiple publications (PMID:30420357
  • PMID:30305285) confirm NTT as a cancer mutation hotspot
  • OncoKB curates biological effect as Likely Gain-of-function
Sources
PMID:30420357 ↗PMID:30305285 ↗oncokb ↗
PM2 SupportingThis variant is absent from large population databases. gnomAD v2.1: absent. gnomAD v4.1: 0 alleles out of 1,168,429 (AF = 0.0%). gnomAD-Canada v1.0: absent. The variant meets the PM2 threshold of <0.1% allele frequency in all populations. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: absent
  • gnomAD v4.1: 0/1
  • 168
  • 429 alleles (AF = 0.0%)
  • gnomAD-Canada v1.0: absent
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. BayesDel score is -0.034 (negative scores predict a benign effect). SpliceAI max delta score is 0.02, predicting no splicing impact. REVEL and HCI prior are unavailable but the available in silico tools consistently support a neutral or benign prediction. Details ▾Hide ▴
Evidence considered
  • BayesDel score: -0.034 (predicted benign)
  • SpliceAI max delta: 0.02 (no predicted splice impact)
Still missing
  • REVEL and HCI prior unavailable
  • only 2 of 4 possible in silico tools provided a score.
Sources
bayesdelspliceai ↗

Not met · 6 · evaluated, threshold not reached

PS1 No evidence was identified that a different nucleotide change at c.26 leading to the same p.Gly9Asp amino acid substitution has been classified as pathogenic in a clinical database or the literature. PS1 requires a previously established pathogenic variant producing the same amino acid change via a different nucleotide substitution. Details ▾Hide ▴
Evidence considered
  • No alternate nucleotide change producing p.Gly9Asp found in ClinVar or reviewed publications.
Still missing
  • No alternate nucleotide path to p.Gly9Asp was identified.
PM5 No confirmed pathogenic missense variant at the same amino acid position (Gly9) was identified in ClinVar. The PM5 candidate harvesting pipeline could not confirm any classic same-residue comparator with a pathogenic classification. While G9R was functionally characterized alongside other NTT mutants, it lacks a ClinVar expert panel pathogenic classification. Details ▾Hide ▴
Evidence considered
  • No pathogenic ClinVar classification for any variant at position Gly9 (same residue
  • different amino acid change).
Still missing
  • G9R and other G9 substitutions exist in the literature but lack ClinVar pathogenic classifications.
PP3 In silico tools do not support a damaging effect. BayesDel score is -0.034 (negative scores predict benign). REVEL is unavailable (no coverage for chrX:20138613 in local REVEL database). SpliceAI max delta is 0.02 (no predicted splice impact). HCI prior is unavailable (gene not supported). Multiple computational lines of evidence suggest a neutral or benign effect rather than a damaging one. Details ▾Hide ▴
Evidence considered
  • BayesDel score: -0.034 (predicted benign)
  • SpliceAI max delta: 0.02 (no splice impact)
  • REVEL: unavailable
  • HCI prior: gene not supported
Still missing
  • REVEL and HCI prior unavailable for this variant.
Sources
bayesdelspliceai ↗
BA1 The variant allele frequency in gnomAD v4.1 is 0.0% (0/1,168,429 alleles), well below the BA1 threshold of >1%. This variant is not a common polymorphism. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 AF = 0.0% (0/1
  • 168
  • 429 alleles).
Sources
gnomad_v4 ↗
BS1 The variant allele frequency in gnomAD v4.1 is 0.0% (0/1,168,429 alleles), well below the BS1 threshold of >0.3%. The variant is too rare in the general population to support BS1. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 AF = 0.0% (0/1
  • 168
  • 429 alleles).
Sources
gnomad_v4 ↗
BS3 Functional studies in the literature do not demonstrate a benign effect. Rather, the G9D/R13H double mutant shows reduced Rps10 binding and NTT domain mutants consistently show gain-of-function effects (enhanced scanning, increased translation of cell cycle genes) (PMID:30420357). OncoKB curation also supports Likely Gain-of-function. These findings are inconsistent with a benign functional effect. Details ▾Hide ▴
Evidence considered
  • G9D/R13H double mutant shows reduced Rps10 binding (PMID:30420357
  • Figure 8)
  • NTT domain mutants show enhanced scanning and cell cycle gene translation — consistent with gain-of-function
  • not benign
  • OncoKB: Likely Gain-of-function
Sources
PMID:30420357 ↗oncokb ↗

Not assessed · 13 · no assessment recorded

PS2 No de novo data (parental testing results, trio sequencing) is available for this variant. PS2 cannot be assessed without confirmed de novo observation. Details ▾Hide ▴
Still missing
  • No de novo data available for this case.
PS4 No case-control data or systematically ascertained affected vs. unaffected carrier frequencies are available for this variant. The variant has been observed in COSMIC (6 somatic occurrences) but somatic prevalence does not directly address germline PS4. Details ▾Hide ▴
Evidence considered
  • COSMIC reports 6 somatic occurrences (COSV63309275) but no germline case-control data are available.
Still missing
  • No germline case-control data for EIF1AX c.26G>A.
PM6 No de novo data or confirmed maternity/paternity information is available. PM6 requires a confirmed de novo observation with both parental genotypes confirmed. Details ▾Hide ▴
Still missing
  • No de novo or family data available.
PP1 No cosegregation data with disease in multiple affected family members is available for this variant. Details ▾Hide ▴
Still missing
  • No family or cosegregation data available.
PP2 Insufficient data to determine whether EIF1AX has a low rate of benign missense variation and whether missense variants are a common disease mechanism in a germline context. While EIF1AX missense mutations are established somatic drivers, the germline missense constraint has not been systematically characterized. Details ▾Hide ▴
Evidence considered
  • EIF1AX germline missense constraint not characterized
  • somatic missense enrichment does not directly support PP2.
Still missing
  • No gnomAD missense constraint metric (Z-score) available or evaluated for EIF1AX.
PP4 No proband phenotype or clinical data is available to evaluate phenotype specificity or gene-disease fit. Details ▾Hide ▴
Still missing
  • No proband phenotype data available.
PP5 No reputable source has independently classified this variant as pathogenic for a germline disorder. The ClinVar entry (VCV004539547) classifies it as 'Likely oncogenic' in a somatic context with criteria provided by a single submitter; this does not satisfy PP5 for germline ACMG/AMP interpretation. Details ▾Hide ▴
Evidence considered
  • ClinVar classification is somatic ('Likely oncogenic')
  • not germline pathogenic.
Still missing
  • No independent germline pathogenic classification from a reputable source.
BS2 No data available regarding observation of this variant in healthy adult individuals with full penetrance expected. The absence from gnomAD suggests it is not observed in healthy populations, but this alone does not satisfy the BS2 requirement for confirmed observation in a healthy adult. Details ▾Hide ▴
Still missing
  • No confirmed observation in healthy adults with complete penetrance data.
BS4 No family segregation data is available to evaluate whether the variant does not segregate with disease in affected family members. Details ▾Hide ▴
Still missing
  • No segregation data available.
BP2 No data available on observation of this variant in trans with a known pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant for a recessive disorder. Details ▾Hide ▴
Still missing
  • No in trans/cis data available for EIF1AX c.26G>A.
BP5 No alternative molecular basis for disease has been identified in the available data. No proband or phenotype data are available to evaluate BP5. Details ▾Hide ▴
Still missing
  • No proband data or alternative molecular basis identified.
BP6 No reputable source has classified this variant as benign or likely benign. The ClinVar entry classifies it as 'Likely oncogenic' in a somatic context, which does not inform germline BP6. Details ▾Hide ▴
Still missing
  • No reputable germline benign classification available.
PS5 No evidence was identified from a reputable source (e.g., clinical diagnostic laboratory, expert panel) classifying this variant as pathogenic that is independent of the evidence already evaluated under other criteria. The ClinVar entry (VCV004539547) classifies this variant as 'Likely oncogenic' in a somatic context with a single submitter. Details ▾Hide ▴
Evidence considered
  • ClinVar entry VCV004539547: Likely oncogenic
  • single submitter
  • somatic context.
Still missing
  • No independent germline pathogenic classification from a reputable source.
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_001412.4:c.26G>A is a missense variant (p.Gly9Asp). It does not fall into any default PVS1 null-variant category (nonsense, frameshift, or canonical ±1,2 splice consensus). The generic PVS1 decision framework from PMC6185798 does not apply to this variant class. Details ▾Hide ▴
Evidence considered
  • Missense substitution at c.26G>A does not qualify for PVS1 null-variant buckets.
Sources
pvs1_generic_framework ↗
PM3 N/ANo data context suggesting recessive inheritance or trans configuration with a pathogenic variant. EIF1AX is X-linked and not established as a recessive disease gene. Details ▾Hide ▴

No further detail was recorded.

PM4 N/AVariant is a single-nucleotide substitution, not a protein-length-changing variant (in-frame deletion/insertion, stop-loss, or initiation codon change). Details ▾Hide ▴

No further detail was recorded.

BP1 N/AEIF1AX has both loss-of-function and gain-of-function disease mechanisms described. Germline EIF1AX variants have been reported in uveal melanoma predisposition, and missense mutations in the NTT domain are established somatic oncogenic drivers. BP1 requires that only truncating variants cause disease, which is not the case for EIF1AX. Details ▾Hide ▴
Evidence considered
  • EIF1AX has both GOF and LOF mechanisms
  • NTT missense mutations are established cancer drivers.
Sources
pvs1_gene_context
BP3 N/AVariant is a substitution, not an in-frame deletion or insertion in a repetitive region. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ANM_001412.4:c.26G>A is a missense variant (p.Gly9Asp), not a synonymous or intronic variant. BP7 is only applicable to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
  • Missense variant — BP7 applies only to synonymous/intronic variants.

Identifiers

Gene
EIF1AX
Transcript
NM_001412.4
Coding (HGVS c.)
NM_001412.4:c.26G>A
Protein (HGVS p.)
NP_001403.1:p.(Gly9Asp)
GRCh38
chrX:20138613 C>T
GRCh37
chrX:20156731 C>T
ClinVar
4539547
COSMIC
COSV63309275

Gene diagram

Every interpreted variant in EIF1AX, mapped onto the exon structure of NM_001412.4. Select a row to find it on the plot.

EIF1AXNM_001412.4
Fetching transcript structure from UCSC…
gnomAD v4.1 0 / 1,168,429 alleles AF 0 · 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 0 · 0 / 1,168,429 alleles · 0 hom
No alternate alleles recorded in the displayed ancestry groups.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1168429 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/56125 alleles, homozygotes = 0).

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +3 bp
0.010
SpliceAI acceptor gainat -312 bp
0.000
SpliceAI donor lossat +1 bp
0.020
SpliceAI donor gainat -17 bp
0.010
Pangolin splice lossmagnitude shown
-0.010
Pangolin splice gain
0.010

Other predictors

REVEL
Not available
BayesDel
-0.034

How the predictions were used

BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. BayesDel score is -0.034 (negative scores predict a benign effect). SpliceAI max delta score is 0.02, predicting no splicing impact. REVEL and HCI prior are unavailable but the available in silico tools consistently support a neutral or benign prediction. Details ▾Hide ▴
Evidence considered
  • BayesDel score: -0.034 (predicted benign)
  • SpliceAI max delta: 0.02 (no predicted splice impact)
Still missing
  • REVEL and HCI prior unavailable
  • only 2 of 4 possible in silico tools provided a score.
Sources
bayesdelspliceai ↗
PP3 In silico tools do not support a damaging effect. BayesDel score is -0.034 (negative scores predict benign). REVEL is unavailable (no coverage for chrX:20138613 in local REVEL database). SpliceAI max delta is 0.02 (no predicted splice impact). HCI prior is unavailable (gene not supported). Multiple computational lines of evidence suggest a neutral or benign effect rather than a damaging one. Details ▾Hide ▴
Evidence considered
  • BayesDel score: -0.034 (predicted benign)
  • SpliceAI max delta: 0.02 (no splice impact)
  • REVEL: unavailable
  • HCI prior: gene not supported
Still missing
  • REVEL and HCI prior unavailable for this variant.
Sources
bayesdelspliceai ↗
BP7 N/ANM_001412.4:c.26G>A is a missense variant (p.Gly9Asp), not a synonymous or intronic variant. BP7 is only applicable to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
  • Missense variant — BP7 applies only to synonymous/intronic variants.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). BayesDel score = -0.0342974.

7 paper records listed. 2 cited in the classification.

Cited in the classification

  • EIF1AX and RAS Mutations Cooperate to Drive Thyroid Tumorigenesis through ATF4 and c-MYC.
    Studied EIF1AX mutations in advanced thyroid cancers. Characterized NTT mutants G8R, G9R, and G15V, along with the A113splice CTT hotspot mutation. Demonstrated that EIF1AX NTT mutants have increased affinity for PIC components (EIF2α, EIF5) and increase global protein synthesis. EIF1AX mutations clustered within the first 15 amino acids of the NTT and cooperate with oncogenic RAS to drive thyroid tumorigenesis. G9D was not specifically studied or mentioned.
    → PM1 Does not name this variant
    PMID 30305285 ↗
    Source detail
    NTT mutants (G8R, G9R, G15V) or EIF1AX-c'spl with an antibody to HA showed pulldown of the TC component

    Location Results, paragraph 1: NTT mutants listed (G8R, G9R, G15V). Figure 3: co-IP experiments with NTT mutants. Figure 5: mTOR signaling data.

    Context Co-immunoprecipitation in HEK293T cells; isogenic thyroid cancer cell lines (CAL62, TTA1, C643); Nthy-Ori 3-1 immortalized thyroid cells; mouse models (Tg-rtTA/TRE-EIF1AX-c'spl).

  • Cancer-Associated Eukaryotic Translation Initiation Factor 1A Mutants Impair Rps3 and Rps10 Binding and Enhance Scanning of Cell Cycle Genes.
    Sehrawat U et al. · 2019 Feb 1
    EIF1AX G9D single mutant was generated by site-directed mutagenesis alongside six other NTT mutants. Functional characterization was performed on the G9D/R13H double mutant, which showed reduced binding to ribosomal protein Rps10 in in vitro pull-down assays (not significant for Rps3). The G9R single mutant (same position) showed enhanced translation of long 5'UTR mRNAs in luciferase reporter assays. All seven NTT cancer-associated mutants displayed enhanced scanning compared to wild-type, consistent with a gain-of-function mechanism impairing scanning arrest.
    → PS3 → PM1 Names this variant
    PMID 30420357 ↗
    Source detail
    mutants (G6D, G9D, G9R, G8RG9R, K10E, R13H and G15D) were generated by site directed mutagenesis

    Location Methods (Plasmids section): G9D listed as one of seven NTT mutants generated. Results (Figure 8): G9D/R13H double mutant tested in Rps3/Rps10 binding assays. Figure 7: G8R/G9R and other NTT mutants tested in luciferase reporter and polysome profiling assays.

    Context In vitro binding assays using bacterially expressed His-tagged Rps3/Rps10 with untagged eIF1A mutants; luciferase reporter assays in MEF and HEK293T cells; polysome profiling in HEK293T cells.

Other recorded publications

  • Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.
    Comprehensive genomic characterization of poorly differentiated and anaplastic thyroid cancers by next-generation sequencing of 341 cancer genes. Identified EIF1AX mutations as recurrent in advanced thyroid cancers, enriched in PDTC and ATC. Specific variant-level data not confirmed in the available abstract; full text was not available for review.
    Does not name this variant
    PMID 26878173 ↗
  • Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Variant Interpretation for Cancer Consortium (VICC).
    Horak P et al. · 2022
    Joint ClinGen/CGC/VICC recommendations for classification of somatic variants in cancer. Defines standards for oncogenicity classification. Does not mention EIF1AX or any specific variant.
    Does not name this variant
    PMID 35101336 ↗
  • Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.
    Schrijver I et al. · 2012
    Association for Molecular Pathology report on clinical diagnostic genome sequencing. Reviews NGS technologies, bioinformatics challenges, and clinical applications for inherited conditions and cancer. Does not mention EIF1AX or any specific variant.
    Does not name this variant
    PMID 22918138 ↗
  • Chromosomal microarray analysis, including constitutional and neoplastic disease applications, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).
    Shao L et al. · 2021
    ACMG technical standard for chromosomal microarray analysis (2021 revision). Covers validation, verification, and clinical applications of CMA for constitutional and neoplastic disorders. Does not mention EIF1AX or any specific sequence variant.
    Does not name this variant
    PMID 34131312 ↗
  • American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.
    Cooley LD et al. · 2013
    ACMG technical standards and guidelines for microarray analysis in neoplastic disorders (2013). Covers chromosomal microarray technologies for cancer applications. Does not mention EIF1AX or any specific sequence variant.
    Does not name this variant
    PMID 23619274 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 0 / 1,168,429 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.020 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

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; MAF= 0.00000%, 0/1168429 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/56125 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 but submission details could not be extracted. (ClinVarID = 4539547)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). BayesDel score = -0.0342974.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.

Somatic

This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV63309275, n = 6 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.