3-169765003-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NR_001566.1(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_001566.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:2B:7

Conservation

PhyloP100: -0.00500

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:

Genome browser will be placed here

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/exons	MANE	UniProt
TERC	NR_001566.1 linkuse as main transcript	n.58G>A		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.45G>A		non_coding_transcript_exon_variant	1/1
TERC	ENST00000602385.1 linkuse as main transcript	n.58G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2420

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00378

AC:

875

AN:

231422

Hom.:

AF XY:

0.00299

AC XY:

382

AN XY:

127830

show subpopulations

Gnomad AFR exome

AF:

0.0564

Gnomad AMR exome

AF:

0.00219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000990

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000741

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.00203

AC:

1242

AN:

613090

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

515

AN XY:

335118

show subpopulations

Gnomad4 AFR exome

AF:

0.0553

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000829

Gnomad4 OTH exome

AF:

0.00340

GnomAD4 genome

AF:

0.0159

AC:

2423

AN:

152356

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1137

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0555

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0182

Asia WGS

AF:

0.00375

AC:

AN:

3478

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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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

Invitae

Jan 29, 2024

- -

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.92

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.2

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