rs756967332
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NR_001566.1(TERC):n.191C>T 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 0.00000495 in 606,462 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: not found (cov: 32)
Exomes 𝑓: 0.0000049 ( 0 hom. )
Consequence
TERC
NR_001566.1 non_coding_transcript_exon
NR_001566.1 non_coding_transcript_exon
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.768
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERC | NR_001566.1 | n.191C>T | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
Telomerase-vert | ENST00000363312.1 | n.178C>T | non_coding_transcript_exon_variant | 1/1 | |||||
TERC | ENST00000602385.1 | n.191C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000463 AC: 1AN: 215772Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 119922
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GnomAD4 exome AF: 0.00000495 AC: 3AN: 606462Hom.: 0 Cov.: 0 AF XY: 0.00000302 AC XY: 1AN XY: 331210
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GnomAD4 genome ? Cov.: 32
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Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 12, 2022 | DNA sequence analysis of the TERC gene demonstrated a sequence change in exon 1, n.191C>T. This change does not appear to have been previously described in individuals with TERC-related disorders. This sequence change has been described in the gnomAD database in one individual which corresponds to a population frequency of 0.00046% (dbSNP rs756967332). This sequence change affects a poorly conserved nucleotide located in a domain that is not known to be functional. The functional significance of this sequence change is not known at present and its contribution to this individual's disease phenotype cannot definitively be determined. - |
Dyskeratosis congenita, autosomal dominant 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2023 | This variant occurs in the TERC gene, which encodes an RNA molecule that does not result in a protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TERC-related conditions. ClinVar contains an entry for this variant (Variation ID: 465763). This variant is located within the template/pseudoknot domain of the TERC RNA component, which is required for RNA or RNP stability (PMID: 15082312, 21844345). This variant is located in a region of TERC in which a significant number of disease causing variants have been reported (PMID: 15082312, 21844345, 21931702). These observations suggest that this may be a clinically significant region. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at