rs1553915517

Variant names:

• chr3-169763862-ATCCTAAGGAATTGAAGGTATGGATTTGGGACGGAATTACCTTGTCGTGATAAGTGGGCAGAATGGCCTGTTTGTTTCTTTCAACCTAGTGGGCCATTAGCTTATTTTCTTAAAGGAAATCAGAGCCAATTCTTGTGGGAGACTGCCGGCTGGGAGGGTTGGGGGTGGGGGGTGTGGAATAAATTTCTTTTCCGTCTTTCATTATGCCTAGTGTTCCGTTATTGGAACGCTAAGCTTGTGGGGGTTATATCCTACTGCTCAAGGTCATCGCCAAGGTCTAATTTTTCAAAAAAGAAACTTCTAACCTCTGGCATAAACCGATGACCATTAAAGGAACACAATTTCCAATGTTCATTTAGATCTTCTAATTAAATATTCATTAAATGTTAAATGATCTCTCAAAAAAAAATGACTGTTCTCCCACACCCCGTTGAGGGGACTGGTCGAGATCTACCTTGGGAGAAGCAAAAACCTCAACAAAATCTGCAGAGCAGGAACTAAGTTGTAATACAACCATAAAAGGCAACAAAAAGCGGAAGACGGGAGAACCCACGCAGGAACGGCTCCAGGCAACCCCGGCTCACTGCCCATTCATTTTGGCCGACTTTGGAGGTGCCTTCACGTCTCCTGCCAATTTGCAGCACACTGGCCCAGTCAGTCAGGTTTGGGGGTTCACAAGCCCCCATTGCCGGCGAGGGGTGACGGATGCGCACGATCGGCGTTCCCCCCACCAACAGGAAAGCGAACTGCATGTGTGAGCCGAGTCCTGGGTGCACGTCCCACAGCTCAGGGAATCGCGCCGCGCGCGGGGACTCGCTCCGT-A
• ENST00000602385.3:n.378_*747del

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP5_Moderate

The ENST00000602385.3(TERC):​n.378_*747del variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TERC ENST00000602385.3 splice_region, non_coding_transcript_exon
• Clinical Significance: Pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 0.617
• Publications: 0 publications found

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]

TERC Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal dominant 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ENSG00000296372 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP5: Variant 3-169763862-ATCCTAAGGAATTGAAGGTATGGATTTGGGACGGAATTACCTTGTCGTGATAAGTGGGCAGAATGGCCTGTTTGTTTCTTTCAACCTAGTGGGCCATTAGCTTATTTTCTTAAAGGAAATCAGAGCCAATTCTTGTGGGAGACTGCCGGCTGGGAGGGTTGGGGGTGGGGGGTGTGGAATAAATTTCTTTTCCGTCTTTCATTATGCCTAGTGTTCCGTTATTGGAACGCTAAGCTTGTGGGGGTTATATCCTACTGCTCAAGGTCATCGCCAAGGTCTAATTTTTCAAAAAAGAAACTTCTAACCTCTGGCATAAACCGATGACCATTAAAGGAACACAATTTCCAATGTTCATTTAGATCTTCTAATTAAATATTCATTAAATGTTAAATGATCTCTCAAAAAAAAATGACTGTTCTCCCACACCCCGTTGAGGGGACTGGTCGAGATCTACCTTGGGAGAAGCAAAAACCTCAACAAAATCTGCAGAGCAGGAACTAAGTTGTAATACAACCATAAAAGGCAACAAAAAGCGGAAGACGGGAGAACCCACGCAGGAACGGCTCCAGGCAACCCCGGCTCACTGCCCATTCATTTTGGCCGACTTTGGAGGTGCCTTCACGTCTCCTGCCAATTTGCAGCACACTGGCCCAGTCAGTCAGGTTTGGGGGTTCACAAGCCCCCATTGCCGGCGAGGGGTGACGGATGCGCACGATCGGCGTTCCCCCCACCAACAGGAAAGCGAACTGCATGTGTGAGCCGAGTCCTGGGTGCACGTCCCACAGCTCAGGGAATCGCGCCGCGCGCGGGGACTCGCTCCGT-A is Pathogenic according to our data. Variant chr3-169763862-ATCCTAAGGAATTGAAGGTATGGATTTGGGACGGAATTACCTTGTCGTGATAAGTGGGCAGAATGGCCTGTTTGTTTCTTTCAACCTAGTGGGCCATTAGCTTATTTTCTTAAAGGAAATCAGAGCCAATTCTTGTGGGAGACTGCCGGCTGGGAGGGTTGGGGGTGGGGGGTGTGGAATAAATTTCTTTTCCGTCTTTCATTATGCCTAGTGTTCCGTTATTGGAACGCTAAGCTTGTGGGGGTTATATCCTACTGCTCAAGGTCATCGCCAAGGTCTAATTTTTCAAAAAAGAAACTTCTAACCTCTGGCATAAACCGATGACCATTAAAGGAACACAATTTCCAATGTTCATTTAGATCTTCTAATTAAATATTCATTAAATGTTAAATGATCTCTCAAAAAAAAATGACTGTTCTCCCACACCCCGTTGAGGGGACTGGTCGAGATCTACCTTGGGAGAAGCAAAAACCTCAACAAAATCTGCAGAGCAGGAACTAAGTTGTAATACAACCATAAAAGGCAACAAAAAGCGGAAGACGGGAGAACCCACGCAGGAACGGCTCCAGGCAACCCCGGCTCACTGCCCATTCATTTTGGCCGACTTTGGAGGTGCCTTCACGTCTCCTGCCAATTTGCAGCACACTGGCCCAGTCAGTCAGGTTTGGGGGTTCACAAGCCCCCATTGCCGGCGAGGGGTGACGGATGCGCACGATCGGCGTTCCCCCCACCAACAGGAAAGCGAACTGCATGTGTGAGCCGAGTCCTGGGTGCACGTCCCACAGCTCAGGGAATCGCGCCGCGCGCGGGGACTCGCTCCGT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 7319.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERC	NR_001566.3	n.378_*747del		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1
TERC	NR_001566.3	n.378_*747del		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TERC	ENST00000602385.3	n.378_*747del		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000296372	ENST00000738610.1	n.-523_298del		non_coding_transcript_exon_variant	Exon 1 of 1
ENSG00000296372	ENST00000738610.1	n.-523_298del		upstream_gene_variant
TERC	ENST00000602385.3	n.378_*747del		downstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

Submissions by phenotype

Dyskeratosis congenita, autosomal dominant 1 Pathogenic:3

May 10, 2012

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

- -

Sep 27, 2001

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 dyskeratosis congenita (PMID: 11574891; internal data). It has also been observed to segregate with disease in related individuals. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located within the BoxH/ACA scaRNA domain of the TERC RNA component, which is required for telomerase activity (PMID: 21844345). For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr3-169481650;