20-63694428-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001283009.2(RTEL1):c.3049G>T(p.Asp1017Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D1017N) has been classified as Likely benign.
Frequency
Consequence
NM_001283009.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.3049G>T | p.Asp1017Tyr | missense_variant | Exon 31 of 35 | 5 | NM_001283009.2 | ENSP00000353332.5 | ||
RTEL1 | ENST00000508582.7 | c.3121G>T | p.Asp1041Tyr | missense_variant | Exon 31 of 35 | 2 | ENSP00000424307.2 | |||
RTEL1 | ENST00000370018.7 | c.3049G>T | p.Asp1017Tyr | missense_variant | Exon 31 of 35 | 1 | ENSP00000359035.3 | |||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*651G>T | non_coding_transcript_exon_variant | Exon 28 of 35 | 5 | ENSP00000457428.1 | ||||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*651G>T | 3_prime_UTR_variant | Exon 28 of 35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460072Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726274
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1017 of the RTEL1 protein (p.Asp1017Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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