rs138576158
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001283009.2(RTEL1):āc.3107C>Gā(p.Thr1036Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000414 in 1,594,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001283009.2 missense, splice_region
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.3107C>G | p.Thr1036Arg | missense_variant, splice_region_variant | 31/35 | ENST00000360203.11 | NP_001269938.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.3107C>G | p.Thr1036Arg | missense_variant, splice_region_variant | 31/35 | 5 | NM_001283009.2 | ENSP00000353332.5 | ||
RTEL1 | ENST00000508582.7 | c.3179C>G | p.Thr1060Arg | missense_variant, splice_region_variant | 31/35 | 2 | ENSP00000424307.2 | |||
RTEL1 | ENST00000370018.7 | c.3107C>G | p.Thr1036Arg | missense_variant, splice_region_variant | 31/35 | 1 | ENSP00000359035.3 | |||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*709C>G | splice_region_variant, non_coding_transcript_exon_variant | 28/35 | 5 | ENSP00000457428.1 | ||||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*709C>G | 3_prime_UTR_variant | 28/35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152232Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000821 AC: 20AN: 243572Hom.: 0 AF XY: 0.0000528 AC XY: 7AN XY: 132666
GnomAD4 exome AF: 0.0000381 AC: 55AN: 1441992Hom.: 0 Cov.: 31 AF XY: 0.0000350 AC XY: 25AN XY: 714238
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152232Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74378
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2024 | In silico analysis indicates that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Has not been previously published as pathogenic or benign to our knowledge - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jul 30, 2022 | This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 1036 of the RTEL1 protein (p.Thr1036Arg). This variant is present in population databases (rs138576158, gnomAD 0.2%). 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:c.3179C>G (p.Thr1060Arg). ClinVar contains an entry for this variant (Variation ID: 572880). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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, criteria provided, single submitter | curation | Sema4, Sema4 | Aug 19, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at