rs587776876
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PP5_Very_Strong
The NR_001566.1(TERC):n.54_57del variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: not found (cov: 32)
Consequence
TERC
NR_001566.1 non_coding_transcript_exon
NR_001566.1 non_coding_transcript_exon
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.588
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 Pathogenic. Variant got 10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-169765003-CAGTT-C is Pathogenic according to our data. Variant chr3-169765003-CAGTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 30265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-169765003-CAGTT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TERC | NR_001566.1 | n.54_57del | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
Telomerase-vert | ENST00000363312.1 | n.41_44del | non_coding_transcript_exon_variant | 1/1 | |||||
TERC | ENST00000602385.1 | n.54_57del | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dyskeratosis congenita, autosomal dominant 1 Pathogenic:3
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 09, 2012 | - - |
Pathogenic, no assertion criteria provided | curation | GeneReviews | May 10, 2012 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2020 | 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 (ExAC no frequency). This variant has been observed in individual(s) with dyskeratosis congenita (DC) and with clinical features of DC (PMID: 22341970, 16332973, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30265). 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). Functional studies testing the effect of this variant on TERC secondary structure or function have not been reported. For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 24, 2023 | PP4, PM1, PM2_supporting, PS3, PS4_moderate - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at