chrX-154763383-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001363.5(DKC1):c.16+402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00458 in 112,488 control chromosomes in the GnomAD database, including 1 homozygotes. There are 176 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0046 ( 1 hom., 176 hem., cov: 24)
Consequence
DKC1
NM_001363.5 intron
NM_001363.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.40
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant X-154763383-G-A is Benign according to our data. Variant chrX-154763383-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1702762.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00458 (515/112488) while in subpopulation NFE AF= 0.00562 (299/53195). AF 95% confidence interval is 0.0051. There are 1 homozygotes in gnomad4. There are 176 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DKC1 | NM_001363.5 | c.16+402G>A | intron_variant | ENST00000369550.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DKC1 | ENST00000369550.10 | c.16+402G>A | intron_variant | 1 | NM_001363.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00460 AC: 517AN: 112436Hom.: 2 Cov.: 24 AF XY: 0.00509 AC XY: 176AN XY: 34580
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00458 AC: 515AN: 112488Hom.: 1 Cov.: 24 AF XY: 0.00508 AC XY: 176AN XY: 34642
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 18, 2022 | See Variant Classification Assertion Criteria. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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