Variant chrX-154763383-G-A details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

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:

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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 Hemizygotes in GnomAd4 at 176 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKC1	NM_001363.5 linkuse as main transcript	c.16+402G>A		intron_variant		ENST00000369550.10	NP_001354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DKC1	ENST00000369550.10 linkuse as main transcript	c.16+402G>A		intron_variant		1	NM_001363.5	ENSP00000358563	P2	O60832-1

Frequencies

GnomAD3 genomes

AF:

0.00460

AC:

517

AN:

112436

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

176

AN XY:

34580

show subpopulations

Gnomad AFR

AF:

0.000582

Gnomad AMI

AF:

0.0162

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00566

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.0209

Gnomad NFE

AF:

0.00562

Gnomad OTH

AF:

0.00658

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00458

AC:

515

AN:

112488

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

176

AN XY:

34642

show subpopulations

Gnomad4 AFR

AF:

0.000581

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00566

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.00562

Gnomad4 OTH

AF:

0.00651

Alfa

AF:

0.00626

Hom.:

Bravo

AF:

0.00319

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.9

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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