NM_198253.3:c.2468+10G>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_198253.3(TERT):c.2468+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
TERT
NM_198253.3 intron
NM_198253.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00700
Publications
0 publications found
Genes affected
TERT (HGNC:11730): (telomerase reverse transcriptase) Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity. [provided by RefSeq, Jul 2008]
TERT Gene-Disease associations (from GenCC):
- pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- dyskeratosis congenita, autosomal dominant 2Inheritance: AR, AD, SD, Unknown Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
- acute myeloid leukemiaInheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- dyskeratosis congenitaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Hoyeraal-Hreidarsson syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- melanoma, cutaneous malignant, susceptibility to, 9Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 5-1271109-C-T is Benign according to our data. Variant chr5-1271109-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1895837.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.2468+10G>A | intron_variant | Intron 8 of 15 | ENST00000310581.10 | NP_937983.2 | ||
TERT | NM_001193376.3 | c.2468+10G>A | intron_variant | Intron 8 of 14 | NP_001180305.1 | |||
TERT | NR_149162.3 | n.2366-2476G>A | intron_variant | Intron 6 of 12 | ||||
TERT | NR_149163.3 | n.2330-2476G>A | intron_variant | Intron 6 of 12 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459472Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725950 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1459472
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
725950
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44696
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26118
East Asian (EAS)
AF:
AC:
0
AN:
39690
South Asian (SAS)
AF:
AC:
0
AN:
85846
European-Finnish (FIN)
AF:
AC:
0
AN:
52184
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111364
Other (OTH)
AF:
AC:
0
AN:
60342
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
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>80
Age
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Idiopathic Pulmonary Fibrosis;C3151443:Dyskeratosis congenita, autosomal dominant 2 Benign:1
Dec 28, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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