About TERT
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TERT c.3184G>A, p.(Ala1062Thr)
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: 3
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 3
BA1Stand alone
BA1 · stand alone
This variant is common in population databases. The gnomAD v2.1 allele frequency is 1.24601% and the gnomAD v4.1 allele frequency is 1.94967%, both above the benign stand-alone threshold of 1.0%.
BS1Strong
BS1 · strong
Population frequency is greater than expected for a pathogenic TERT germline variant. The gnomAD v2.1 allele frequency is 1.24601% and the gnomAD v4.1 allele frequency is 1.94967%, both above the BS1 threshold of 0.3%.
BP4Supporting
BP4 · supporting
Multiple computational results support a benign effect. REVEL is 0.207 and BayesDel is -0.373519, both favoring a tolerated missense change, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01.
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: BA1 stand-alone benign, BS1 strong benign, BP4 supporting benign; combination = 1 stand-alone 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
31,441 / 1,612,636 alleles
gnomAD v4.1: 31,441 / 1,612,636 alleles. Recorded AF 0.0194967. Recorded homozygote count 363.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0124601; MAF= 1.24601%, 3466/278168 alleles, homozygotes = 44) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0214947; MAF= 2.14947%, 2726/126822 alleles, homozygotes = 40); grpmax FAF= 0.0209994.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
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. TERT is an enzyme that functions to maintain telomere length and genomic stability. The TERT promoter is frequently mutated in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
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.
28 criteria with recorded statuses: 3 met · 4 not met · 13 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The TERT NM_198253.2:c.3184G>A (p.Ala1062Thr) variant has been reported in ClinVar, where most submissions classify it as benign or likely benign.
This variant is common in population databases, with allele frequencies of 1.24601% in gnomAD v2.1 and 1.94967% in gnomAD v4.1, which are above the benign stand-alone threshold of 1.0% and above the BS1 threshold of 0.3%.
In silico prediction does not support a damaging effect, with REVEL 0.207, BayesDel -0.373519, and SpliceAI maximum delta score 0.01 predicting no significant splice impact.
No criteria match.
Met · 3
BA1 Stand aloneThis variant is common in population databases. The gnomAD v2.1 allele frequency is 1.24601% and the gnomAD v4.1 allele frequency is 1.94967%, both above the benign stand-alone threshold of 1.0%. Details ▾Hide ▴
BS1 StrongPopulation frequency is greater than expected for a pathogenic TERT germline variant. The gnomAD v2.1 allele frequency is 1.24601% and the gnomAD v4.1 allele frequency is 1.94967%, both above the BS1 threshold of 0.3%. Details ▾Hide ▴
BP4 SupportingMultiple computational results support a benign effect. REVEL is 0.207 and BayesDel is -0.373519, both favoring a tolerated missense change, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01. Details ▾Hide ▴
Evidence considered
- REVEL 0.207
- BayesDel -0.373519
- SpliceAI max delta 0.01
Sources
Not met · 4 · evaluated, threshold not reached
PS4 Although this variant has been reported in disease literature and ClinVar, it is also common in population databases, with gnomAD v2.1 AF 1.24601% and gnomAD v4.1 AF 1.94967%, both well above the PM2 rarity threshold of 0.1%. These frequencies do not support enrichment in affected individuals sufficient for PS4. Details ▾Hide ▴
Evidence considered
- ClinVar reports and literature references
- Population frequency substantially above rarity threshold
Sources
PM1 This variant does not lie in a statistically significant hotspot, and no well-established critical region without benign variation was identified for residue Ala1062 from the reviewed sources. Details ▾Hide ▴
PM2 This variant is not absent or rare in population databases. Its gnomAD v2.1 allele frequency is 1.24601% and its gnomAD v4.1 allele frequency is 1.94967%, both above the PM2 threshold of 0.1%. Details ▾Hide ▴
PP3 Available computational evidence does not support a deleterious effect. REVEL is 0.207, BayesDel is -0.373519, and SpliceAI shows a maximum delta score of 0.01, which predicts no significant splice impact. Details ▾Hide ▴
Evidence considered
- REVEL 0.207
- BayesDel -0.373519
- SpliceAI max delta 0.01
Sources
Not assessed · 13 · no assessment recorded
PS1 No evidence was identified that another nucleotide change causing the same amino acid substitution has already been established as pathogenic or likely pathogenic. Details ▾Hide ▴
Still missing
- A complete same-amino-acid pathogenic variant check was not available from the reviewed sources.
PS2 No confirmed de novo occurrence with verified maternity and paternity was identified for this variant. Details ▾Hide ▴
Still missing
- No parental testing data were identified.
PS3 Published TERT functional literature was identified, but the reviewed materials did not provide a well-established variant-specific functional assay result for p.(Ala1062Thr) that could be used to support a damaging effect. Details ▾Hide ▴
Evidence considered
- ClinVar-linked TERT functional literature
- No reviewed variant-specific damaging assay result in current materials
Still missing
- Direct review of variant-specific functional assay data would be needed to determine whether PS3 can be applied.
Sources
PM3 No evidence was identified for occurrence in trans with a pathogenic variant in a recessive disease context. Details ▾Hide ▴
Still missing
- No phase data or recessive case data were identified.
PM5 No reviewed evidence established a different pathogenic missense change at the same amino acid residue that could support PM5. Details ▾Hide ▴
Still missing
- A residue-specific pathogenic variant review was not available from the reviewed sources.
PM6 No assumed de novo occurrence without confirmed parentage was identified for this variant. Details ▾Hide ▴
Still missing
- No parental testing or limited de novo reports were identified.
PP1 No segregation data were identified for this variant. Details ▾Hide ▴
Still missing
- No informative family segregation reports were identified.
PP4 No case-specific phenotype information was identified that is highly specific for a single genetic etiology and sufficient to support PP4. Details ▾Hide ▴
Still missing
- Phenotype details for the tested individual were not available.
BS2 This variant is observed in multiple homozygotes in gnomAD, but the reviewed materials did not provide gene-specific penetrance or phenotype context needed to determine whether BS2 should be applied for TERT-related disease. Details ▾Hide ▴
Evidence considered
- 44 homozygotes in gnomAD v2.1
- 363 homozygotes in gnomAD v4.1
Still missing
- Gene-specific penetrance and homozygote interpretation guidance were not available in the reviewed sources.
Sources
BS3 Published TERT functional literature was identified, but the reviewed materials did not provide a well-established variant-specific functional assay result for p.(Ala1062Thr) demonstrating normal function that would support BS3. Details ▾Hide ▴
Evidence considered
- ClinVar-linked TERT functional literature
- No reviewed variant-specific normal-function assay result in current materials
Still missing
- Direct review of variant-specific benign functional assay data would be needed to determine whether BS3 can be applied.
Sources
BS4 No non-segregation data were identified for this variant. Details ▾Hide ▴
Still missing
- No informative family data showing lack of segregation were identified.
BP2 No phase data were identified to determine whether this variant occurs in trans with a pathogenic variant for a dominant disorder or in cis with another variant. Details ▾Hide ▴
Still missing
- No phasing information was identified.
BP5 No alternate molecular explanation for a specific reported phenotype was identified for the individual under evaluation. Details ▾Hide ▴
Still missing
- Case-specific phenotype and alternate-cause information were not available.
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is a missense substitution, not a nonsense, frameshift, or canonical splice-site variant. Generic PVS1 is therefore not applicable for this change. Details ▾Hide ▴
Evidence considered
- Missense change p.(Ala1062Thr)
- Generic PVS1 scaffold did not support application
Sources
PM4 N/AThis variant is a missense substitution and does not cause a protein length change. Details ▾Hide ▴
Evidence considered
- Missense change p.(Ala1062Thr)
PP2 N/ANo gene-specific evidence was identified that TERT is a gene in which missense variation is a common established mechanism and benign missense variation is uncommon enough to support PP2. Details ▾Hide ▴
No further detail was recorded.
PP5 N/APP5 is not applied because this criterion relies on external assertions without independently reviewable evidence. Details ▾Hide ▴
No further detail was recorded.
BP1 N/ABP1 is not applicable because missense variation in TERT has been reported in disease-associated contexts, so this is not a gene where only truncating variants are clearly established as pathogenic. Details ▾Hide ▴
Evidence considered
- Published disease-associated TERT missense variants
Sources
BP3 N/AThis is not an in-frame insertion or deletion in a repetitive region. Details ▾Hide ▴
No further detail was recorded.
BP6 N/ABP6 is not applied because this criterion relies on external assertions without independently reviewable evidence. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 is not applicable because this is a missense variant rather than a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Missense change p.(Ala1062Thr)
Identifiers
- Gene
- TERT
- Transcript
- NM_198253.2
- Coding (HGVS c.)
- NM_198253.2:c.3184G>A
- Protein (HGVS p.)
- NP_937983.2:p.(Ala1062Thr)
- GRCh38
- chr5:1254479 C>T
- GRCh37
- chr5:1254594 C>T
Gene diagram
Every interpreted variant in TERT, mapped onto the exon structure of NM_198253.2. Select a row to find it on the plot.
TERTNM_198253.2
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 TERT
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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
31,441 / 1,612,636 alleles
AF 0.0195 · 363 homozygotes · FAF 0.024
gnomAD v2.1
3,466 / 278,168 alleles
AF 0.0125 · 44 homozygotes · FAF 0.021
By genetic ancestry
gnomAD v4.1
AF 0.019 · 31441 / 1,612,636 alleles · 363 hom · FAF 0.024
| European (non-Finnish)28644 / 1,179,840 | 0.024340 hom |
| Remaining individuals1097 / 62,482 | 0.01812 hom |
| Amish15 / 910 | 0.0161 hom |
| European (Finnish)850 / 62,876 | 0.0147 hom |
| Admixed American307 / 59,986 | 0.0051 |
| African/African American252 / 75,014 | 0.00341 hom |
| South Asian211 / 91,052 | 0.00232 hom |
| Ashkenazi Jewish59 / 29,578 | 0.002 |
| Middle Eastern3 / 6,044 | 0.0005 |
| East Asian3 / 44,854 | 6.7e-05 |
gnomAD v2.1
AF 0.012 · 3466 / 278,168 alleles · 44 hom · FAF 0.021
| European (non-Finnish)2726 / 126,822 | 0.02140 hom |
| Remaining individuals103 / 7,090 | 0.0151 hom |
| European (Finnish)332 / 24,850 | 0.0131 hom |
| Admixed American144 / 35,242 | 0.0041 |
| African/African American71 / 23,892 | 0.003 |
| Ashkenazi Jewish25 / 10,256 | 0.0024 |
| South Asian64 / 30,562 | 0.00212 hom |
| East Asian1 / 19,454 | 5.1e-05 |
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.0194967; MAF= 1.94967%, 31441/1612636 alleles, homozygotes = 363) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0242779; MAF= 2.42779%, 28644/1179840 alleles, homozygotes = 340); grpmax FAF= 0.024042.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0124601; MAF= 1.24601%, 3466/278168 alleles, homozygotes = 44) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0214947; MAF= 2.14947%, 2726/126822 alleles, homozygotes = 40); grpmax FAF= 0.0209994.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingMultiple computational results support a benign effect. REVEL is 0.207 and BayesDel is -0.373519, both favoring a tolerated missense change, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.01. Details ▾Hide ▴
Evidence considered
- REVEL 0.207
- BayesDel -0.373519
- SpliceAI max delta 0.01
Sources
PP3 Available computational evidence does not support a deleterious effect. REVEL is 0.207, BayesDel is -0.373519, and SpliceAI shows a maximum delta score of 0.01, which predicts no significant splice impact. Details ▾Hide ▴
Evidence considered
- REVEL 0.207
- BayesDel -0.373519
- SpliceAI max delta 0.01
Sources
BP7 N/ABP7 is not applicable because this is a missense variant rather than a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Missense change p.(Ala1062Thr)
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.207. BayesDel score = -0.373519.
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
31,441 / 1,612,636 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
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/variation/39121/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/5-1254594-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr5-1254479-C-T?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_198253.2%3Ac.3184…
- OncoKB ↗www.oncokb.org/gene/TERT/A1062T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=111747240
- 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= 0.0194967; MAF= 1.94967%, 31441/1612636 alleles, homozygotes = 363) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0242779; MAF= 2.42779%, 28644/1179840 alleles, homozygotes = 340); grpmax FAF= 0.024042.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.0124601; MAF= 1.24601%, 3466/278168 alleles, homozygotes = 44) and has highest observed frequency in the European (non-Finnish) population (AF= 0.0214947; MAF= 2.14947%, 2726/126822 alleles, homozygotes = 40); grpmax FAF= 0.0209994.
ClinVar
This variant has been reported in ClinVar as Benign (10 clinical laboratories) and as Likely benign (6 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Likely Benign (1 clinical laboratory).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.207. BayesDel score = -0.373519.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. TERT is an enzyme that functions to maintain telomere length and genomic stability. The TERT promoter is frequently mutated in various cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV57200744, n = 7 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.