About TERT
No gene-level summary was recorded for this case.
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.
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.No gene-level summary was recorded for this case.
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
The applied criteria and their strengths are shown as assessed under the stated framework.
No pathogenic criterion marked as applied in the recorded assessment.
This variant is common in the general population. gnomAD v2.1 grpmax FAF is 0.656% (South Asian), and gnomAD v4.1 grpmax FAF is 0.728% (Ashkenazi Jewish). Both far exceed the 0.3% BS1 threshold. Observed in 2 homozygotes in v2.1 and 16 homozygotes in v4.1, confirming this is a common benign polymorphism.
Observed in 16 homozygotes in gnomAD v4.1 and 2 homozygotes in gnomAD v2.1. Homozygous occurrence in a general population database is incompatible with a highly penetrant telomere biology disorder whether inherited in a dominant or recessive pattern.
Multiple in silico tools uniformly predict no impact: REVEL score 0.176 (well within benign range), BayesDel score 0.124 (benign range), and SpliceAI max delta 0.00 (no predicted splicing alteration). All computational evidence supports a benign interpretation.
NM_198253.2:c.2517G>A is a synonymous variant (p.Thr839=) with SpliceAI max delta score of 0.00, confirming no predicted impact on splicing. The variant does not create or disrupt a canonical splice site. BP7 is met at supporting level.
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 benign, BP7 supporting benign; combination = 2 strong benign + 2 supporting benign, which maps to Benign.
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1: 3,755 / 1,613,422 alleles. Recorded AF 0.00232735. Recorded homozygote count 16.
This variant is present in gnomAD v2.1 (AF= 0.00267744; MAF= 0.26774%, 754/281612 alleles, homozygotes = 2) and has highest observed frequency in the South Asian population (AF= 0.00735006; MAF= 0.73501%, 225/30612 alleles, homozygotes = 1); grpmax FAF= 0.00656256.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0028773072747014113, 53/18420 alleles, homozygotes = 1).
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
8 Likely benign · 7 Benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
This variant has previously been reported in somatic cancers (COSMIC; COSV104395555, n = 2 times).
This variant does not lie in a statistically significant hotspot.
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 4 met · 10 not met · 0 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
NM_198253.2:c.2517G>A (p.Thr839=) is a synonymous variant in TERT exon 9.
This variant is common in population databases: gnomAD v2.1 AF 0.268% with 2 homozygotes, grpmax FAF 0.656% (BS1).
gnomAD v4.1 confirms high frequency: AF 0.233% with 16 homozygotes, grpmax FAF 0.728% (BS1).
Sixteen homozygotes observed in gnomAD v4.1, incompatible with a highly penetrant telomere biology disorder whether dominant or recessive (BS2).
Multiple in silico tools predict no functional impact: REVEL 0.176, BayesDel 0.124, SpliceAI max delta 0.00 (BP4).
Synonymous variant with no predicted splice alteration; SpliceAI max delta 0.00 (BP7).
ClinVar reports Likely benign (8 laboratories) and Benign (7 laboratories); however, review status is 1-star (criteria provided, single submitter), precluding application of BP6.
No functional studies, segregation data, case-control evidence, or de novo observations were identified for this variant in any reviewed source.
Classification: Benign. Two strong benign criteria (BS1, BS2) and two supporting benign criteria (BP4, BP7) are met. No pathogenic criteria are met.
No criteria match.
Every interpreted variant in TERT, mapped onto the exon structure of NM_198253.2. Select a row to find it on the plot.
| Protein | Location | Classification | Link |
|---|
| Ashkenazi Jewish230 / 29,608 | 0.00783 hom |
| South Asian706 / 91,084 | 0.00788 hom |
| Middle Eastern41 / 6,062 | 0.00682 hom |
| European (Finnish)388 / 63,258 | 0.0061 |
| Remaining individuals178 / 62,502 | 0.00281 hom |
| European (non-Finnish)2154 / 1,180,012 | 0.00182 hom |
| Admixed American34 / 60,028 | 0.00057 |
| African/African American24 / 75,068 | 0.00032 |
| South Asian225 / 30,612 | 0.00741 hom |
| Ashkenazi Jewish71 / 10,308 | 0.0069 |
| European (Finnish)170 / 25,114 | 0.0068 |
| European (non-Finnish)256 / 128,192 | 0.0021 hom |
| Remaining individuals12 / 7,206 | 0.0017 |
| Admixed American13 / 35,394 | 0.00037 |
| African/African American6 / 24,844 | 0.00024 |
| East Asian1 / 19,942 | 5e-05 |
This variant is present in gnomAD v4.1 (AF= 0.00232735; MAF= 0.23274%, 3755/1613422 alleles, homozygotes = 16) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00776817; MAF= 0.77682%, 230/29608 alleles, homozygotes = 3); grpmax FAF= 0.00727701.
This variant is present in gnomAD v2.1 (AF= 0.00267744; MAF= 0.26774%, 754/281612 alleles, homozygotes = 2) and has highest observed frequency in the South Asian population (AF= 0.00735006; MAF= 0.73501%, 225/30612 alleles, homozygotes = 1); grpmax FAF= 0.00656256.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0028773072747014113, 53/18420 alleles, homozygotes = 1).
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.176. BayesDel score = 0.124075.
7 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.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
This variant is present in gnomAD v4.1 (AF= 0.00232735; MAF= 0.23274%, 3755/1613422 alleles, homozygotes = 16) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00776817; MAF= 0.77682%, 230/29608 alleles, homozygotes = 3); grpmax FAF= 0.00727701.
This variant is present in gnomAD v2.1 (AF= 0.00267744; MAF= 0.26774%, 754/281612 alleles, homozygotes = 2) and has highest observed frequency in the South Asian population (AF= 0.00735006; MAF= 0.73501%, 225/30612 alleles, homozygotes = 1); grpmax FAF= 0.00656256.
This variant is present in gnomAD-Canada v1.0 (AF= 0.0028773072747014113, 53/18420 alleles, homozygotes = 1).
This variant has been reported in ClinVar as Likely benign (8 clinical laboratories) and as Benign (7 clinical laboratories). (ClinVarID = 263107)
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.176. BayesDel score = 0.124075.
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV104395555, n = 2 times).
This variant does not lie in a statistically significant hotspot.