3-169765003-C-T
Variant names:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NR_001566.3(TERC):n.58G>A 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 0.00479 in 765,446 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.016 ( 52 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 24 hom. )
Consequence
TERC
NR_001566.3 non_coding_transcript_exon
NR_001566.3 non_coding_transcript_exon
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00500
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 3-169765003-C-T is Benign according to our data. Variant chr3-169765003-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 7323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-169765003-C-T is described in Lovd as [Benign]. Variant chr3-169765003-C-T is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERC | NR_001566.3 | n.58G>A | non_coding_transcript_exon_variant | Exon 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0159 AC: 2420AN: 152238Hom.: 52 Cov.: 32
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GnomAD3 exomes AF: 0.00378 AC: 875AN: 231422Hom.: 17 AF XY: 0.00299 AC XY: 382AN XY: 127830
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GnomAD4 exome AF: 0.00203 AC: 1242AN: 613090Hom.: 24 Cov.: 0 AF XY: 0.00154 AC XY: 515AN XY: 335118
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GnomAD4 genome AF: 0.0159 AC: 2423AN: 152356Hom.: 52 Cov.: 32 AF XY: 0.0153 AC XY: 1137AN XY: 74502
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Pathogenic:2Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 27, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 26, 2017 | c.58G>A in TERC: This variant is not expected to have clinical significance beca use it has been identified in 5.6% (1269/22484) of African chromosomes by the Ge nome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs113 4787931). In addition, in vitro functional assays of telomerase activity show no loss of function with this variant (Ly 2003, Marrone 2004). ACMG/AMP Criteria a pplied: BA1, BS3. - |
Aplastic anemia Pathogenic:1
Pathogenic, no assertion criteria provided | curation | GeneReviews | May 10, 2012 | - - |
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 22, 2002 | - - |
Dyskeratosis congenita, autosomal dominant 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2;C4551974:Dyskeratosis congenita, autosomal dominant 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 08, 2022 | - - |
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