rs746411863
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001283009.2(RTEL1):c.640A>T(p.Asn214Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,613,720 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. N214N) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.640A>T | p.Asn214Tyr | missense_variant | 8/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.1467A>T | non_coding_transcript_exon_variant | 8/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.640A>T | p.Asn214Tyr | missense_variant | 8/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152040Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000251 AC: 63AN: 251484Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135916
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461680Hom.: 0 Cov.: 30 AF XY: 0.0000371 AC XY: 27AN XY: 727142
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152040Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4AN XY: 74250
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 5;C4225346:Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 214 of the RTEL1 protein (p.Asn214Tyr). This variant is present in population databases (rs746411863, 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.712A>T (p.Asn238Tyr). ClinVar contains an entry for this variant (Variation ID: 565342). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | RTEL1 NM_032957.4 exon 8 p.Asn238Tyr (c.712A>T): This variant has not been reported in the literature, but it is present in 0.2% (62/34418) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/20-62298847-A-T). Computational predictive tools suggest that this variant may impact the protein, although evolutionary conservation is unclear. In summary, data on this variant are insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Dyskeratosis congenita, autosomal dominant 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 12, 2020 | - - |
Dyskeratosis congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 06, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at