chr20-63659407-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001283009.2(RTEL1):c.5C>A(p.Pro2His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P2P) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
RTEL1
NM_001283009.2 missense
NM_001283009.2 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 6.93
Genes affected
RTEL1 (HGNC:15888): (regulator of telomere elongation helicase 1) This gene encodes a DNA helicase which functions in the stability, protection and elongation of telomeres and interacts with proteins in the shelterin complex known to protect telomeres during DNA replication. Mutations in this gene have been associated with dyskeratosis congenita and Hoyerall-Hreidarsson syndrome. Read-through transcription of this gene into the neighboring downstream gene, which encodes tumor necrosis factor receptor superfamily, member 6b, generates a non-coding transcript. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.822
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTEL1 | NM_001283009.2 | c.5C>A | p.Pro2His | missense_variant | 2/35 | ENST00000360203.11 | |
RTEL1-TNFRSF6B | NR_037882.1 | n.832C>A | non_coding_transcript_exon_variant | 2/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTEL1 | ENST00000360203.11 | c.5C>A | p.Pro2His | missense_variant | 2/35 | 5 | NM_001283009.2 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | RTEL1: PM2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;.
Polyphen
D;D;D;.;.
Vest4
MutPred
Loss of catalytic residue at P2 (P = 0.0016);Loss of catalytic residue at P2 (P = 0.0016);Loss of catalytic residue at P2 (P = 0.0016);Loss of catalytic residue at P2 (P = 0.0016);Loss of catalytic residue at P2 (P = 0.0016);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at