rs1277188982
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NR_001566.3(TERC):n.202T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 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 Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000033 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TERC
NR_001566.3 non_coding_transcript_exon
NR_001566.3 non_coding_transcript_exon
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0260
Genes affected
TERC (HGNC:11727): (telomerase RNA component) 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, and an RNA component, encoded by this gene, that 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. Mutations in this gene cause autosomal dominant dyskeratosis congenita, and may also be associated with some cases of aplastic anemia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TERC | NR_001566.3 | n.202T>C | non_coding_transcript_exon_variant | Exon 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000333 AC: 2AN: 601232Hom.: 0 Cov.: 0 AF XY: 0.00000610 AC XY: 2AN XY: 328074
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GnomAD4 genome 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
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ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Pulmonary fibrosis Pathogenic:1
| Likely risk allele, no assertion criteria provided | research | Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center | Jun 09, 2022 | Leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted - |
Dyskeratosis congenita, autosomal dominant 1 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2023 | This variant occurs in the TERC gene, which encodes an RNA molecule that does not result in a protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TERC-related conditions. This variant is located within the hypervariable region that is not conserved in the TERC RNA component (PMID: 10721988, 21844345). The functional significance of this region is not well understood. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 465765). - |
TERC-related disorder Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2023 | The TERC n.202T>C is a noncoding alteration. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as uncertain significance or likely risk allele in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/465765/). A similar variant, n.202T>G, was reported in the homozygous state in two affected siblings with pulmonary fibrosis, nail dystrophy, abnormal skin pigmentation, and leukoplakia; however, further segregation studies in additional affected family members were not available (Family 18, Collopy et al. 2015. PubMed ID: 26024875). Functional studies showed that the n.202T>G variant possesses ~92% of wild-type telomerase activity (Collopy et al. 2015. PubMed ID: 26024875). At this time, the clinical significance of the n.202T>C variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at