20-63659448-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001283009.2(RTEL1):c.46C>T(p.Gln16*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001283009.2 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.46C>T | p.Gln16* | stop_gained | Exon 2 of 35 | 5 | NM_001283009.2 | ENSP00000353332.5 | ||
RTEL1 | ENST00000508582.7 | c.46C>T | p.Gln16* | stop_gained | Exon 2 of 35 | 2 | ENSP00000424307.2 | |||
RTEL1 | ENST00000370018.7 | c.46C>T | p.Gln16* | stop_gained | Exon 2 of 35 | 1 | ENSP00000359035.3 | |||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.46C>T | non_coding_transcript_exon_variant | Exon 1 of 35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with RTEL1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln16*) in the RTEL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RTEL1 are known to be pathogenic (PMID: 23453664, 23959892, 25607374). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.