rs148621466
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001283009.2(RTEL1):c.3329T>A(p.Phe1110Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,612,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.3329T>A | p.Phe1110Tyr | missense_variant | Exon 32 of 35 | 5 | NM_001283009.2 | ENSP00000353332.5 | ||
RTEL1 | ENST00000508582.7 | c.3401T>A | p.Phe1134Tyr | missense_variant | Exon 32 of 35 | 2 | ENSP00000424307.2 | |||
RTEL1 | ENST00000370018.7 | c.3329T>A | p.Phe1110Tyr | missense_variant | Exon 32 of 35 | 1 | ENSP00000359035.3 | |||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*931T>A | non_coding_transcript_exon_variant | Exon 29 of 35 | 5 | ENSP00000457428.1 | ||||
RTEL1-TNFRSF6B | ENST00000492259.6 | n.*931T>A | 3_prime_UTR_variant | Exon 29 of 35 | 5 | ENSP00000457428.1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151920Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000205 AC: 5AN: 244346Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133294
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460140Hom.: 0 Cov.: 35 AF XY: 0.0000110 AC XY: 8AN XY: 726350
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151920Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74218
ClinVar
Submissions by phenotype
not provided Uncertain:2
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Uncertain:2
This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 1110 of the RTEL1 protein (p.Phe1110Tyr). This variant is present in population databases (rs148621466, gnomAD 0.004%). 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: 436595). 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. -
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not specified Uncertain:1
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Dyskeratosis congenita Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at