rs200505378
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001283009.2(RTEL1):c.2662G>A(p.Val888Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,610,786 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V888L) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.2662G>A | p.Val888Met | missense_variant | 29/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.3489G>A | non_coding_transcript_exon_variant | 29/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.2662G>A | p.Val888Met | missense_variant | 29/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000523 AC: 13AN: 248776Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135258
GnomAD4 exome AF: 0.0000446 AC: 65AN: 1458456Hom.: 0 Cov.: 31 AF XY: 0.0000496 AC XY: 36AN XY: 725150
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74476
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 | Jan 20, 2024 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 888 of the RTEL1 protein (p.Val888Met). This variant is present in population databases (rs200505378, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. This variant is also known as NM_032957.4(RTEL1):c.2734G>A (p.Val912Met). ClinVar contains an entry for this variant (Variation ID: 573172). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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