Variant rs1800533 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001363.5(DKC1):c.*6G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,182,442 control chromosomes in the GnomAD database, including 5,806 homozygotes. There are 44,397 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 516 hom., 3149 hem., cov: 23)

Exomes 𝑓: 0.11 ( 5290 hom. 41248 hem. )

Consequence

DKC1
NM_001363.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.43

Variant links:

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]

DKC1 links:

DKC1 (HGNC:):

DKC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-154776873-G-A is Benign according to our data. Variant chrX-154776873-G-A is described in ClinVar as [Benign]. Clinvar id is 166995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-154776873-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKC1	NM_001363.5 linkuse as main transcript	c.*6G>A		3_prime_UTR_variant	15/15	ENST00000369550.10	NP_001354.1	O60832-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKC1	ENST00000369550.10 linkuse as main transcript	c.*6G>A		3_prime_UTR_variant	15/15	1	NM_001363.5	ENSP00000358563.5		O60832-1

Frequencies

GnomAD3 genomes

AF:

0.0916

AC:

10180

AN:

111102

Hom.:

516

Cov.:

AF XY:

0.0945

AC XY:

3147

AN XY:

33306

show subpopulations

Gnomad AFR

AF:

0.0271

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.0606

Gnomad MID

AF:

0.148

Gnomad NFE

AF:

0.0927

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.147

AC:

23600

AN:

161034

Hom.:

1515

AF XY:

0.163

AC XY:

8330

AN XY:

51120

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.353

Gnomad FIN exome

AF:

0.0673

Gnomad NFE exome

AF:

0.0950

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.109

AC:

116583

AN:

1071289

Hom.:

5290

Cov.:

AF XY:

0.121

AC XY:

41248

AN XY:

340227

show subpopulations

Gnomad4 AFR exome

AF:

0.0247

Gnomad4 AMR exome

AF:

0.249

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.0641

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.0699

Gnomad4 NFE exome

AF:

0.0896

Gnomad4 OTH exome

AF:

0.128

GnomAD4 genome

AF:

0.0915

AC:

10172

AN:

111153

Hom.:

516

Cov.:

AF XY:

0.0944

AC XY:

3149

AN XY:

33365

show subpopulations

Gnomad4 AFR

AF:

0.0271

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.0606

Gnomad4 NFE

AF:

0.0927

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.0957

Hom.:

1315

Bravo

AF:

0.0954

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 28, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 27% of patients studied by a panel of primary immunodeficiencies. Number of patients: 26. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dyskeratosis congenita, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.17

DANN

Benign

0.59

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over