rs371353556
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP7
The NM_001283009.2(RTEL1):c.2547C>T(p.Gly849=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000515 in 1,398,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G849G) has been classified as Likely benign.
Frequency
Consequence
NM_001283009.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.2547C>T | p.Gly849= | synonymous_variant | 27/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.3374C>T | non_coding_transcript_exon_variant | 27/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.2547C>T | p.Gly849= | synonymous_variant | 27/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152164Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 exomes AF: 0.0000257 AC: 4AN: 155424Hom.: 0 AF XY: 0.0000363 AC XY: 3AN XY: 82600
GnomAD4 exome AF: 0.0000515 AC: 72AN: 1398110Hom.: 0 Cov.: 33 AF XY: 0.0000507 AC XY: 35AN XY: 689908
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74332
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 | Sep 03, 2022 | This sequence change affects codon 849 of the RTEL1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RTEL1 protein. This variant is present in population databases (rs371353556, gnomAD 0.009%). 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: 540931). 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, 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