chr3-169765003-C-T

Position:

• chr3-169765003-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:2 B:7
• Conservation: PhyloP100: -0.00500

Genes affected

Telomerase-vert (HGNC:):

ACMG classification

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	Protein	UniProt
TERC	NR_001566.1	n.58G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
Telomerase-vert	ENST00000363312.1	n.45G>A		non_coding_transcript_exon_variant	1/1	6
TERC	ENST00000602385.1	n.58G>A		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2420 AN: 152238 Hom.: 52 Cov.: 32

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.: 17 AF XY: 0.00299 AC XY: 382 AN XY: 127830

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.: 24 Cov.: 0 AF XY: 0.00154 AC XY: 515 AN XY: 335118

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.: 52 Cov.: 32 AF XY: 0.0153 AC XY: 1137 AN XY: 74502

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.: 5

Bravo AF: 0.0182

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:2 Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
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+	-	- -

not specified Benign:2

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. -
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. -

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

Labcorp Genetics (formerly Invitae), Labcorp

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	11
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

Other links and lift over

dbSNP: rs113487931; hg19: chr3-169482791;