Variant 3-169764547-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000602385.1(TERC):n.514A>G 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 0.263 in 645,400 control chromosomes in the GnomAD database, including 26,589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4450 hom., cov: 33)

Exomes 𝑓: 0.28 ( 22139 hom. )

Consequence

TERC
ENST00000602385.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.65

Variant links:

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 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=-0.8).

BP6

Variant 3-169764547-T-C is Benign according to our data. Variant chr3-169764547-T-C is described in ClinVar as [Benign]. Clinvar id is 440330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TERC	ENST00000602385.1 linkuse as main transcript	n.514A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32394

AN:

152096

Hom.:

4447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0666

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.562

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.278

AC:

137234

AN:

493184

Hom.:

22139

Cov.:

AF XY:

0.277

AC XY:

72597

AN XY:

262432

show subpopulations

Gnomad4 AFR exome

AF:

0.0661

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.612

Gnomad4 SAS exome

AF:

0.279

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.213

AC:

32399

AN:

152216

Hom.:

4450

Cov.:

AF XY:

0.218

AC XY:

16238

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0665

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.562

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.264

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.160

Hom.:

387

Bravo

AF:

0.214

Asia WGS

AF:

0.371

AC:

1289

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 58% of patients studied by a panel of primary immunodeficiencies. Number of patients: 55. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 01, 2016	- -

Dyskeratosis congenita, autosomal dominant 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

DANN

Benign

0.46

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