20-63692814-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001283009.2(RTEL1):āc.2662G>Cā(p.Val888Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,610,786 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_001283009.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.2662G>C | p.Val888Leu | missense_variant | 29/35 | ENST00000360203.11 | NP_001269938.1 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.3489G>C | non_coding_transcript_exon_variant | 29/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.2662G>C | p.Val888Leu | missense_variant | 29/35 | 5 | NM_001283009.2 | ENSP00000353332 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152212Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.000695 AC: 173AN: 248776Hom.: 0 AF XY: 0.000909 AC XY: 123AN XY: 135258
GnomAD4 exome AF: 0.000332 AC: 484AN: 1458456Hom.: 4 Cov.: 31 AF XY: 0.000479 AC XY: 347AN XY: 725150
GnomAD4 genome AF: 0.000223 AC: 34AN: 152330Hom.: 2 Cov.: 33 AF XY: 0.000363 AC XY: 27AN XY: 74476
ClinVar
Submissions by phenotype
Dyskeratosis congenita Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 29, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
RTEL1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 16, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at