Variant rs1060502986 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NR_001566.1(TERC):n.451C>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 0.00000188 in 531,884 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: 0.0000019 ( 0 hom. )

Consequence

TERC
NR_001566.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

Telomerase-vert (HGNC:):

Telomerase-vert links:

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 links:

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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=-0.64).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TERC	NR_001566.1 linkuse as main transcript	n.451C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
Telomerase-vert	ENST00000363312.1 linkuse as main transcript	n.438C>T		non_coding_transcript_exon_variant	1/1
TERC	ENST00000602385.1 linkuse as main transcript	n.451C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000574

AC:

AN:

174084

Hom.:

AF XY:

0.00

AC XY:

AN XY:

95734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000659

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000188

AC:

AN:

531884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

286024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000286

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Dyskeratosis congenita, autosomal dominant 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 15, 2023

This variant occurs in the TERC gene, which encodes an RNA molecule that does not result in a protein product. 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. This variant is located within the BoxH/ACA scaRNA domain of the TERC RNA component, which is required for telomerase activity (PMID: 21844345). ClinVar contains an entry for this variant (Variation ID: 410642). This variant has not been reported in the literature in individuals affected with TERC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over