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TERTc.2765T>ANot classified
Print report
Variant interpretation report

TERT c.2765T>A, p.(Met922Lys)

NM_198253.2:c.2765T>A NP_937983.2:p.(Met922Lys) View identifiers
Classification
Not classified

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. Select a step to read what it means.

Not classified yet.Select a step to read what it means.

In plain language

Gene-level background from the recorded interpretation.

About TERT

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: 1 Benign evidence criteria: 0
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting

Absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases, meeting the allele frequency threshold of <0.1% for PM2 under generic ACMG/AMP guidelines.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Not classified

No source classification-combination explanation was recorded.

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
0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. 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

In progress — evidence not uploaded yet.

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
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

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

26 criteria with recorded statuses: 1 met · 23 not met · 0 not assessed · 2 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_198253.2:c.2765T>A (p.Met922Lys) is a missense variant in TERT, a gene in which loss-of-function is an established mechanism for autosomal dominant telomere biology disorders including dyskeratosis congenita and familial melanoma.

This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (allele frequency 0%), meeting PM2 at supporting strength.

Computational predictors are inconclusive or lean benign: REVEL score 0.409 (below 0.5 threshold), BayesDel score -0.101837 (benign range), and SpliceAI max delta 0.00 (no predicted splice impact). PP3 is not met.

This variant has not been reported in ClinVar, COSMIC, or the published literature; no functional, segregation, or case-control data are available.

PM2 (supporting) is the only met criterion. No pathogenic criteria above supporting strength are met, and no benign criteria are triggered. Under the ACMG/AMP 2015 generic classification framework, a single supporting criterion is insufficient to reach Likely Pathogenic. This variant is classified as a Variant of Uncertain Significance (VUS).

Met · 1

PM2 SupportingAbsent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases, meeting the allele frequency threshold of <0.1% for PM2 under generic ACMG/AMP guidelines. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1: allele count 0
  • absent
  • gnomAD v4.1: allele count 0
  • gnomAD-Canada v1.0: allele count 0
Sources
gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

Not met · 23 · evaluated, threshold not reached

PS1 No different pathogenic missense change at amino acid position 922 (Met922) has been identified in ClinVar or published literature. Details ▾Hide ▴
Evidence considered
  • ClinVar contains no entry for any variant at this residue
Still missing
  • No same-residue comparator variants identified in any database
Sources
clinvar ↗
PS2 No de novo observation data available for this variant. Details ▾Hide ▴
Still missing
  • No segregation or parent-of-origin data available
PS3 No well-established functional studies demonstrate a damaging effect for this variant. OncoKB reports Unknown Oncogenic Effect with no variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
  • OncoKB classification: Unknown Oncogenic Effect
  • No variant-specific functional publications identified
Still missing
  • No in vitro or in vivo functional data for M922K
Sources
oncokb ↗
PS4 No case-control data available comparing variant prevalence in affected versus unaffected individuals. Details ▾Hide ▴
Still missing
  • No disease cohort data available
PM1 Not located in a statistically significant mutational hotspot (CancerHotspots.org) and no domain-level functional evidence has been presented to support PM1 at this residue. Details ▾Hide ▴
Evidence considered
  • CancerHotspots: residue not significant
  • No mutational cluster detected at position 922
Still missing
  • No TERT domain-specific functional annotation available to assess PM1 independently
PM5 No pathogenic variant at the same amino acid residue (Met922) with a different amino acid change has been identified in ClinVar; PM5 candidate search returned zero same-residue candidates. Details ▾Hide ▴
Evidence considered
  • PM5 candidate search: 0 same-residue candidates found
  • ClinVar: no entries for any variant at residue 922
Still missing
  • No comparator missense variant at Met922 identified
Sources
pm5_candidatesclinvar ↗
PM6 No de novo observation data available for this variant. Details ▾Hide ▴
Still missing
  • No de novo data from trio sequencing or published reports
PP1 No co-segregation data available for this variant in affected families. Details ▾Hide ▴
Still missing
  • No family co-segregation data
PP2 TERT missense constraint data (HCI prior) is not available for this gene; insufficient data to assess whether TERT has a low rate of benign missense variation and high rate of pathogenic missense variation. Details ▾Hide ▴
Evidence considered
  • HCI prior: gene not supported
  • no probability score available
Still missing
  • No TERT missense constraint metrics (Z-score
  • HCI prior) available to apply PP2
PP3 Multiple lines of computational evidence do not support a deleterious effect: REVEL score 0.409 is below the 0.5 pathogenicity threshold, BayesDel score -0.101837 falls in the benign range, and SpliceAI predicts no splicing impact (max delta = 0.00). Details ▾Hide ▴
Evidence considered
  • REVEL: 0.409 (intermediate
  • below 0.5 threshold)
  • BayesDel: -0.101837 (benign range)
  • SpliceAI: max delta 0.00 (no predicted splice impact)
Sources
revelbayesdelspliceai ↗
PP4 No patient phenotype or clinical data available for this variant. Details ▾Hide ▴
Still missing
  • No clinical phenotype data associated with this variant
PP5 Not reported as pathogenic by a reputable source; this variant is absent from ClinVar. Details ▾Hide ▴
Evidence considered
  • ClinVar: variant absent
  • no submissions
Sources
clinvar ↗
BA1 Allele frequency is 0% across all gnomAD populations, well below the 1% BA1 threshold. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 AF: 0%
  • gnomAD v4.1 AF: 0%
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 Allele frequency is 0% across all gnomAD populations, well below the 0.3% BS1 threshold. Details ▾Hide ▴
Evidence considered
  • gnomAD v2.1 AF: 0%
  • gnomAD v4.1 AF: 0%
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS2 No evidence of this variant observed in a homozygous state in healthy adults. Details ▾Hide ▴
Evidence considered
  • gnomAD homozygote count: 0 across all datasets
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS3 No well-established functional studies demonstrate a benign effect for this variant; no variant-specific functional data is available. Details ▾Hide ▴
Evidence considered
  • OncoKB: Unknown Oncogenic Effect
  • no functional data
Still missing
  • No in vitro or in vivo functional data for M922K
Sources
oncokb ↗
BS4 No segregation data available for this variant in affected families. Details ▾Hide ▴
Still missing
  • No family segregation data
BP1 Although TERT loss-of-function is a supported germline disease mechanism, TERT-related telomere biology disorders are caused by both truncating and missense pathogenic variants. The evidence does not demonstrate that TERT disease is primarily caused by truncating variants to the exclusion of missense changes. Details ▾Hide ▴
Evidence considered
  • TERT LoF mechanism supported for telomere biology disorders
  • Both truncating and missense pathogenic variants reported in TERT
Still missing
  • No systematic assessment of TERT missense vs. truncating pathogenic variant distribution
Sources
pvs1_gene_context
BP2 No evidence of this variant observed in trans with a known pathogenic variant. Details ▾Hide ▴
Still missing
  • No trans-phase observation data
BP4 Computational evidence is mixed and does not provide multiple lines of strong support for a benign impact. REVEL 0.409 is intermediate, BayesDel -0.101837 weakly supports benign, and SpliceAI max delta 0.00 indicates no splicing effect. This does not meet the threshold for BP4, which requires multiple lines of computational evidence all suggesting no impact. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.409 (intermediate
  • not clearly benign)
  • BayesDel: -0.101837 (weakly benign)
  • SpliceAI: max delta 0.00 (no splicing impact)
Sources
revelbayesdelspliceai ↗
BP5 No evidence that this variant is found in a case with an alternate molecular basis for disease. Details ▾Hide ▴
Still missing
  • No co-occurrence data with a known pathogenic variant in the same gene or pathway
BP6 Not reported as benign by a reputable source; this variant is absent from ClinVar. Details ▾Hide ▴
Evidence considered
  • ClinVar: variant absent
  • no submissions
Sources
clinvar ↗
PS5 No data meeting PS5 criteria; variant is absent from ClinVar and no published reports of segregation or de novo occurrence. Details ▾Hide ▴
Evidence considered
  • ClinVar: no entry for this variant
Still missing
  • No variant-specific reports in databases or literature
Sources
clinvar ↗
Not applicable · 2· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AMissense variant (p.Met922Lys) does not fall into null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus variants); not eligible for PVS1 under the ClinGen SVI generic PVS1 framework (PMC6185798). Details ▾Hide ▴
Evidence considered
  • Variant class is missense (substitution)
  • Variant bucket: 'other' per pvs1_variant_assessment
  • apply_generic_pvs1_framework: false
Sources
pvs1_generic_frameworkpvs1_variant_assessment
BP7 N/ABP7 applies only to synonymous variants. NM_198253.2:c.2765T>A is a missense variant (p.Met922Lys). Details ▾Hide ▴
Evidence considered
  • Variant is missense
  • not synonymous

Identifiers

Gene
TERT
Transcript
NM_198253.2
Coding (HGVS c.)
NM_198253.2:c.2765T>A
Protein (HGVS p.)
NP_937983.2:p.(Met922Lys)
GRCh38
chr5:1264482 A>T
GRCh37
chr5:1264597 A>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…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 0 / 0 alleles AF 0 · 0 homozygotes

By genetic ancestry

gnomAD-Canada

AF 0 · 0 / 0 alleles · 0 hom

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.

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown
-0.000
Pangolin splice gain
0.000

Other predictors

REVEL
0.409
BayesDel
-0.102

How the predictions were used

PP3 Multiple lines of computational evidence do not support a deleterious effect: REVEL score 0.409 is below the 0.5 pathogenicity threshold, BayesDel score -0.101837 falls in the benign range, and SpliceAI predicts no splicing impact (max delta = 0.00). Details ▾Hide ▴
Evidence considered
  • REVEL: 0.409 (intermediate
  • below 0.5 threshold)
  • BayesDel: -0.101837 (benign range)
  • SpliceAI: max delta 0.00 (no predicted splice impact)
Sources
revelbayesdelspliceai ↗
BP4 Computational evidence is mixed and does not provide multiple lines of strong support for a benign impact. REVEL 0.409 is intermediate, BayesDel -0.101837 weakly supports benign, and SpliceAI max delta 0.00 indicates no splicing effect. This does not meet the threshold for BP4, which requires multiple lines of computational evidence all suggesting no impact. Details ▾Hide ▴
Evidence considered
  • REVEL: 0.409 (intermediate
  • not clearly benign)
  • BayesDel: -0.101837 (weakly benign)
  • SpliceAI: max delta 0.00 (no splicing impact)
Sources
revelbayesdelspliceai ↗
BP7 N/ABP7 applies only to synonymous variants. NM_198253.2:c.2765T>A is a missense variant (p.Met922Lys). Details ▾Hide ▴
Evidence considered
  • Variant is missense
  • not synonymous

Statement

In silico

In progress — evidence not uploaded yet.

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

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

In progress — evidence not uploaded yet.

In silico

In progress — evidence not uploaded yet.

Functional

In progress — evidence not uploaded yet.

Somatic

In progress — evidence not uploaded yet.

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Literature

In progress — evidence not uploaded yet.