rs398123019
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001283009.2(RTEL1):c.751G>A(p.Glu251Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001283009.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.751G>A | p.Glu251Lys | missense_variant | 9/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.1578G>A | non_coding_transcript_exon_variant | 9/38 | |||
LOC124904954 | XR_007067717.1 | n.733-58C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.751G>A | p.Glu251Lys | missense_variant | 9/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432356Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 709460
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 5 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 07, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 30, 2017 | - - |
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 | Oct 30, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 251 of the RTEL1 protein (p.Glu251Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with dyskeratosis congenita (PMID: 23453664). This variant is also known as p.Gly275Lys. ClinVar contains an entry for this variant (Variation ID: 42022). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at