Variant X-23000170-A-G 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.113A>G(p.His38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,199,935 control chromosomes in the GnomAD database, including 4 homozygotes. There are 219 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., 100 hem., cov: 23)

Exomes 𝑓: 0.00039 ( 4 hom. 119 hem. )

Consequence

DDX53
NM_182699.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0590

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=0.0036946237).

BP6

Variant X-23000170-A-G is Benign according to our data. Variant chrX-23000170-A-G is described in ClinVar as [Benign]. Clinvar id is 724376.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 100 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX53	NM_182699.4 linkuse as main transcript	c.113A>G	p.His38Arg	missense_variant	1/1	ENST00000327968.7	NP_874358.2	Q86TM3
PTCHD1-AS	NR_073010.2 linkuse as main transcript	n.343+63868T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX53	ENST00000327968.7 linkuse as main transcript	c.113A>G	p.His38Arg	missense_variant	1/1	6	NM_182699.4	ENSP00000368667.2	Q86TM3
ENSG00000289084	ENST00000687119.1 linkuse as main transcript	n.83-56022T>C		intron_variant
ENSG00000289084	ENST00000687248.1 linkuse as main transcript	n.343+63868T>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

397

AN:

112341

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

100

AN XY:

34485

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00122

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000938

Gnomad OTH

AF:

0.00398

GnomAD3 exomes

AF:

0.00102

AC:

175

AN:

172358

Hom.:

AF XY:

0.000691

AC XY:

AN XY:

57898

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.000428

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000385

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.000385

AC:

419

AN:

1087541

Hom.:

Cov.:

AF XY:

0.000335

AC XY:

119

AN XY:

354831

show subpopulations

Gnomad4 AFR exome

AF:

0.0115

Gnomad4 AMR exome

AF:

0.000701

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000192

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000598

Gnomad4 OTH exome

AF:

0.000922

GnomAD4 genome

AF:

0.00353

AC:

397

AN:

112394

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

100

AN XY:

34548

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.00122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000938

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.000483

Hom.:

Bravo

AF:

0.00409

ESP6500AA

AF:

0.0128

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00111

AC:

135

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DDX53-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

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

not provided

Benign:1

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

0.065

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.076

DANN

Benign

0.41

DEOGEN2

Benign

0.0021

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.44

REVEL

Benign

0.048

Sift

Benign

0.63

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.037

MVP

0.043

MPC

0.11

ClinPred

0.0032

GERP RS

2.0

Varity_R

0.041

gMVP

0.15

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