3-169764547-T-C

Variant names:

• chr3-169764547-T-C
• rs2293607
• ENST00000738610.1:n.162T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000738610.1(ENSG00000296372):​n.162T>C 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: ENSG00000296372 ENST00000738610.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.65
• Publications: 68 publications found

Genes affected

ENSG00000296372 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TERC	NR_001566.3	n.*63A>G		downstream_gene_variant		ENST00000602385.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296372	ENST00000738610.1	n.162T>C		non_coding_transcript_exon_variant	Exon 1 of 1
TERC	ENST00000602385.3	n.*63A>G		downstream_gene_variant		6	NR_001566.3

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32394 AN: 152096 Hom.: 4447 Cov.: 33

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.: 0 AF XY: 0.277 AC XY: 72597 AN XY: 262432

African (AFR) AF: 0.0661 AC: 878 AN: 13290

American (AMR) AF: 0.427 AC: 10984 AN: 25732

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2578 AN: 14202

East Asian (EAS) AF: 0.612 AC: 20323 AN: 33214

South Asian (SAS) AF: 0.279 AC: 14133 AN: 50710

European-Finnish (FIN) AF: 0.273 AC: 9143 AN: 33472

Middle Eastern (MID) AF: 0.241 AC: 483 AN: 2004

European-Non Finnish (NFE) AF: 0.245 AC: 71768 AN: 292876

Other (OTH) AF: 0.251 AC: 6944 AN: 27684

GnomAD4 genome AF: 0.213 AC: 32399 AN: 152216 Hom.: 4450 Cov.: 33 AF XY: 0.218 AC XY: 16238 AN XY: 74422

African (AFR) AF: 0.0665 AC: 2765 AN: 41560

American (AMR) AF: 0.313 AC: 4785 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 608 AN: 3462

East Asian (EAS) AF: 0.562 AC: 2899 AN: 5158

South Asian (SAS) AF: 0.271 AC: 1306 AN: 4828

European-Finnish (FIN) AF: 0.264 AC: 2799 AN: 10604

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16608 AN: 67986

Other (OTH) AF: 0.224 AC: 474 AN: 2114

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Sep 01, 2016

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Dyskeratosis congenita, autosomal dominant 1 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.46
PhyloP100		-2.7

Splicing

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

Other links and lift over

dbSNP: rs2293607; hg19: chr3-169482335; COSMIC: COSV57754451;