rs151214675
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001283009.2(RTEL1):c.334G>A(p.Ala112Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000149 in 1,613,970 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A112V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001283009.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.334G>A | p.Ala112Thr | missense_variant | 4/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.1161G>A | non_coding_transcript_exon_variant | 4/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.334G>A | p.Ala112Thr | missense_variant | 4/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 151996Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000163 AC: 41AN: 251454Hom.: 1 AF XY: 0.000132 AC XY: 18AN XY: 135914
GnomAD4 exome AF: 0.000144 AC: 211AN: 1461856Hom.: 2 Cov.: 31 AF XY: 0.000161 AC XY: 117AN XY: 727228
GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152114Hom.: 1 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74354
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 17, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 112 of the RTEL1 protein (p.Ala112Thr). This variant is present in population databases (rs151214675, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 436586). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 20, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 28, 2015 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2023 | Observed in individuals with early-onset inflammatory bowel disease, aged-related macular degeneration, or chronic hypersensitivity pneumonitis (Petersen et al., 2017; Ley et al., 2019; Waksmunski et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31367973, 31268371, 28930861) - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at