rs141686314

Variant names:

• chr3-169764833-C-T
• rs141686314
• ENST00000363312.1:n.215G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NR_001566.3(TERC):​n.228G>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 0.00141 in 729,688 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (2 hom.)
• Consequence: TERC NR_001566.3 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:6
• Conservation: PhyloP100: 0.585

Genes affected

Telomerase-vert (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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 3-169764833-C-T is Benign according to our data. Variant chr3-169764833-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 39286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-169764833-C-T is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 682 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TERC	NR_001566.3	n.228G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
Telomerase-vert	ENST00000363312.1	n.215G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
TERC	ENST00000602385.1	n.228G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 683 AN: 152242 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00111 AC: 186 AN: 168058 Hom.: 1 AF XY: 0.000795 AC XY: 74 AN XY: 93028

Gnomad AFR exome AF: 0.0176

Gnomad AMR exome AF: 0.000916

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.000603 AC: 348 AN: 577332 Hom.: 2 Cov.: 0 AF XY: 0.000449 AC XY: 141 AN XY: 314270

Gnomad4 AFR exome AF: 0.0160

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000241

Gnomad4 OTH exome AF: 0.000983

GnomAD4 genome AF: 0.00448 AC: 682 AN: 152356 Hom.: 9 Cov.: 33 AF XY: 0.00412 AC XY: 307 AN XY: 74502

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00162 Hom.: 0

Bravo AF: 0.00492

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dyskeratosis congenita, autosomal dominant 1 Pathogenic:1 Benign:1

Pathogenic, no assertion criteria provided	curation	GeneReviews	May 10, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Dec 11, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 10, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 03, 2016	- -

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

Jul 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.87
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141686314; hg19: chr3-169482621;