rs1289430524
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001363.5(DKC1):c.1346G>A(p.Arg449Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,210,369 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Consequence
DKC1
NM_001363.5 missense
NM_001363.5 missense
Scores
6
3
8
Clinical Significance
Conservation
PhyloP100: 5.90
Genes affected
DKC1 (HGNC:2890): (dyskerin pseudouridine synthase 1) This gene functions in two distinct complexes. It plays an active role in telomerase stabilization and maintenance, as well as recognition of snoRNAs containing H/ACA sequences which provides stability during biogenesis and assembly into H/ACA small nucleolar RNA ribonucleoproteins (snoRNPs). This gene is highly conserved and widely expressed, and may play additional roles in nucleo-cytoplasmic shuttling, DNA damage response, and cell adhesion. Mutations have been associated with X-linked dyskeratosis congenita. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
Missense variant in the DKC1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 22 curated pathogenic missense variants (we use a threshold of 10). The gene has 27 curated benign missense variants. Gene score misZ: 3.3994 (above the threshold of 3.09). GenCC associations: The gene is linked to Hoyeraal-Hreidarsson syndrome, DKC1-related disorder, dyskeratosis congenita, X-linked, dyskeratosis congenita.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000889 AC: 1AN: 112473Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34631
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GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097896Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1AN XY: 363256
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GnomAD4 genome AF: 0.00000889 AC: 1AN: 112473Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1AN XY: 34631
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inherited Immunodeficiency Diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0507);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at