rs779282812
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001283009.2(RTEL1):āc.8A>Cā(p.Lys3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. K3K) has been classified as Likely benign.
Frequency
Consequence
NM_001283009.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.8A>C | p.Lys3Thr | missense_variant | 2/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.835A>C | non_coding_transcript_exon_variant | 2/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.8A>C | p.Lys3Thr | missense_variant | 2/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251334Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135886
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461466Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727078
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces lysine with threonine at codon 3 of the RTEL1 protein (p.Lys3Thr). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is present in population databases (rs779282812, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at