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

2

Clinical Significance

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

Conservation

PhyloP100: -0.00500
Variant links:
Genes affected

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 Protein UniProt
TERCNR_001566.1 linkuse as main transcriptn.58G>A non_coding_transcript_exon_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
Telomerase-vertENST00000363312.1 linkuse as main transcriptn.45G>A non_coding_transcript_exon_variant 1/16
TERCENST00000602385.1 linkuse as main transcriptn.58G>A non_coding_transcript_exon_variant 1/16

Frequencies

GnomAD3 genomes
AF:
0.0159
AC:
2420
AN:
152238
Hom.:
52
Cov.:
32
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.:
17
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.:
24
Cov.:
0
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.:
52
Cov.:
32
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.:
5
Bravo
AF:
0.0182
Asia WGS
AF:
0.00375
AC:
13
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
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 13, 2023- -
Likely benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineDec 26, 2017c.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 submitterclinical testingGeneDxApr 27, 2016This 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 providedcurationGeneReviewsMay 10, 2012- -
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJun 22, 2002- -
Dyskeratosis congenita, autosomal dominant 1 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 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 submitterclinical testingFulgent Genetics, Fulgent GeneticsApr 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs113487931; hg19: chr3-169482791; API