20-63693168-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001283009.2(RTEL1):c.2877C>T(p.His959His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RTEL1
NM_001283009.2 synonymous
NM_001283009.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.396
Publications
0 publications found
Genes affected
RTEL1 (HGNC:15888): (regulator of telomere elongation helicase 1) This gene encodes a DNA helicase which functions in the stability, protection and elongation of telomeres and interacts with proteins in the shelterin complex known to protect telomeres during DNA replication. Mutations in this gene have been associated with dyskeratosis congenita and Hoyerall-Hreidarsson syndrome. Read-through transcription of this gene into the neighboring downstream gene, which encodes tumor necrosis factor receptor superfamily, member 6b, generates a non-coding transcript. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]
RTEL1-TNFRSF6B (HGNC:44095): (RTEL1-TNFRSF6B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RTEL1 (regulator of telomere elongation helicase 1) and TNFRSF6B (tumor necrosis factor receptor superfamily, member 6b, decoy) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 20-63693168-C-T is Benign according to our data. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63693168-C-T is described in CliVar as Likely_benign. Clinvar id is 1534988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.396 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RTEL1 | ENST00000360203.11 | c.2877C>T | p.His959His | synonymous_variant | Exon 30 of 35 | 5 | NM_001283009.2 | ENSP00000353332.5 | ||
| RTEL1 | ENST00000508582.7 | c.2949C>T | p.His983His | synonymous_variant | Exon 30 of 35 | 2 | ENSP00000424307.2 | |||
| RTEL1 | ENST00000370018.7 | c.2877C>T | p.His959His | synonymous_variant | Exon 30 of 35 | 1 | ENSP00000359035.3 | |||
| RTEL1-TNFRSF6B | ENST00000492259.6 | n.*479C>T | non_coding_transcript_exon_variant | Exon 27 of 35 | 5 | ENSP00000457428.1 | ||||
| RTEL1-TNFRSF6B | ENST00000492259.6 | n.*479C>T | 3_prime_UTR_variant | Exon 27 of 35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00 AC: 0AN: 249340 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
249340
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1459978Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726290 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1459978
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726290
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44690
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26104
East Asian (EAS)
AF:
AC:
1
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
52076
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111580
Other (OTH)
AF:
AC:
0
AN:
60332
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dyskeratosis congenita Uncertain:1
Apr 11, 2025
Natera, Inc.
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Benign:1
Jul 12, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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