rs1555811762
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001283009.2(RTEL1):c.2005C>T(p.Gln669Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q669Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001283009.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.2005C>T | p.Gln669Ter | stop_gained | 23/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.2832C>T | non_coding_transcript_exon_variant | 23/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.2005C>T | p.Gln669Ter | stop_gained | 23/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1456836Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 724758
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Pulmonary fibrosis Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Garcia Pulmonary Genetics Research Laboratory, Columbia University Irving Medical Center | Jun 09, 2022 | Pathogenic criteria: null variant (PVS1) with functional study supportive of damaging effect (PS3): leukocyte telomere length (by qPCR) less than 10th percentile age-adjusted - |
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at