Variant X-23000547-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_182699.4(DDX53):c.490G>A(p.Glu164Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,209,165 control chromosomes in the GnomAD database, including 2 homozygotes. There are 478 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., 27 hem., cov: 23)

Exomes 𝑓: 0.0013 ( 2 hom. 451 hem. )

Consequence

DDX53
NM_182699.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0540

Variant links:

Genes affected

DDX53 (HGNC:20083): (DEAD-box helicase 53) This intronless gene encodes a protein which contains several domains found in members of the DEAD-box helicase protein family. Other members of this protein family participate in ATP-dependent RNA unwinding. [provided by RefSeq, Sep 2011]

DDX53 links:

ENSG00000289084 (HGNC:):

ENSG00000289084 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0089791715).

BP6

Variant X-23000547-G-A is Benign according to our data. Variant chrX-23000547-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717072.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-23000547-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX53	NM_182699.4 linkuse as main transcript	c.490G>A	p.Glu164Lys	missense_variant	1/1	ENST00000327968.7	NP_874358.2	Q86TM3
PTCHD1-AS	NR_073010.2 linkuse as main transcript	n.343+63491C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX53	ENST00000327968.7 linkuse as main transcript	c.490G>A	p.Glu164Lys	missense_variant	1/1	6	NM_182699.4	ENSP00000368667.2	Q86TM3
ENSG00000289084	ENST00000687119.1 linkuse as main transcript	n.83-56399C>T		intron_variant
ENSG00000289084	ENST00000687248.1 linkuse as main transcript	n.343+63491C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000817

AC:

AN:

111410

Hom.:

Cov.:

AF XY:

0.000831

AC XY:

AN XY:

33692

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000642

AC:

117

AN:

182349

Hom.:

AF XY:

0.000583

AC XY:

AN XY:

66867

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000537

Gnomad FIN exome

AF:

0.00156

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

AF:

0.00128

AC:

1403

AN:

1097700

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

451

AN XY:

363070

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.000987

Gnomad4 NFE exome

AF:

0.00153

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.000807

AC:

AN:

111465

Hom.:

Cov.:

AF XY:

0.000800

AC XY:

AN XY:

33757

show subpopulations

Gnomad4 AFR

AF:

0.000196

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00116

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.000718

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00173

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00193

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DDX53-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.7

DANN

Benign

0.84

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.46

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

REVEL

Benign

0.024

Sift

Benign

0.30

Sift4G

Benign

0.57

Polyphen

0.089

Vest4

0.043

MVP

0.068

MPC

0.10

ClinPred

0.010

GERP RS

2.0

Varity_R

0.076

gMVP

0.49

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