20-63659410-AG-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001283009.2(RTEL1):c.9delG(p.Ile4fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001283009.2 frameshift
Scores
Clinical Significance
Conservation
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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.9delG | p.Ile4fs | frameshift_variant | Exon 2 of 35 | 5 | NM_001283009.2 | ENSP00000353332.5 | ||
RTEL1 | ENST00000508582.7 | c.9delG | p.Ile4fs | frameshift_variant | Exon 2 of 35 | 2 | ENSP00000424307.2 | |||
RTEL1 | ENST00000370018.7 | c.9delG | p.Ile4fs | frameshift_variant | Exon 2 of 35 | 1 | ENSP00000359035.3 | |||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.9delG | 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
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Pathogenic:1
RTEL1 c.9delG is absent from a large population dataset and has not been reported in ClinVar nor the literature, to our knowledge. This frameshift variant is predicted to lead to a premature stop codon in exon 2 (the first coding exon) of RTEL1, likely leading to nonsense-mediated decay and lack of protein production. We consider RTEL1 c.9delG to be pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.