rs1248582778
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NR_001566.3(TERC):n.36C>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 0.00000657 in 152,226 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
Consequence
NR_001566.3 non_coding_transcript_exon
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TERC | NR_001566.3 | n.36C>T | non_coding_transcript_exon_variant | Exon 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
GnomAD4 exome Cov.: 0
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74362
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal dominant 1 Uncertain:2
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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 been observed in individual(s) with clinical features of dyskeratosis congenita (PMID: 21931702, 29146883, 30426156). ClinVar contains an entry for this variant (Variation ID: 619284). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects TERC function (PMID: 21931702). 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. -
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2 Uncertain:1
This TERC variant is absent from large population datasets. TERC n.36C>T has not been reported in ClinVar, to our knowledge. This variant has been reported in both the heterozygous and homozygous state in individuals with aplastic anemia. The importance of the position of this variant within the TERC pseudoknot/template domain remains unclear, however, it is thought to affect telomerase RNA structure. This has not been confirmed experimentally to our knowledge. The clinical significance of n.36C>T is uncertain at this time. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at