rs2853690
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_198253.3(TERT):c.*99C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 998,776 control chromosomes in the GnomAD database, including 16,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.19 ( 3360 hom., cov: 33)
Exomes 𝑓: 0.16 ( 12833 hom. )
Consequence
TERT
NM_198253.3 3_prime_UTR
NM_198253.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.49
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
?
Variant 5-1253629-G-A is Benign according to our data. Variant chr5-1253629-G-A is described in ClinVar as [Benign]. Clinvar id is 350515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERT | NM_198253.3 | c.*99C>T | 3_prime_UTR_variant | 16/16 | ENST00000310581.10 | ||
TERT | NM_001193376.3 | c.*99C>T | 3_prime_UTR_variant | 15/15 | |||
TERT | NR_149162.3 | n.3206C>T | non_coding_transcript_exon_variant | 13/13 | |||
TERT | NR_149163.3 | n.3170C>T | non_coding_transcript_exon_variant | 13/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TERT | ENST00000310581.10 | c.*99C>T | 3_prime_UTR_variant | 16/16 | 1 | NM_198253.3 | P2 | ||
ENST00000666708.1 | n.289-1045G>A | intron_variant, non_coding_transcript_variant | |||||||
TERT | ENST00000484238.6 | n.1940C>T | non_coding_transcript_exon_variant | 11/11 | 5 | ||||
TERT | ENST00000656021.1 | c.*3044C>T | 3_prime_UTR_variant, NMD_transcript_variant | 17/17 |
Frequencies
GnomAD3 genomes ? AF: 0.193 AC: 29371AN: 152112Hom.: 3357 Cov.: 33
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GnomAD4 exome AF: 0.162 AC: 137406AN: 846546Hom.: 12833 Cov.: 11 AF XY: 0.158 AC XY: 69096AN XY: 437754
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. - |
Aplastic anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Dyskeratosis congenita, autosomal dominant 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at