X-23000457-A-G

Position:

chrX-23000457-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_182699.4(DDX53):c.400A>G(p.Ile134Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,210,189 control chromosomes in the GnomAD database, including 1 homozygotes. There are 107 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 0.00028 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00024 ( 1 hom. 98 hem. )

Consequence

DDX53
NM_182699.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.279

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0146482885).

BP6

Variant X-23000457-A-G is Benign according to our data. Variant chrX-23000457-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2204382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX53	NM_182699.4 linkuse as main transcript	c.400A>G	p.Ile134Val	missense_variant	1/1	ENST00000327968.7	NP_874358.2	Q86TM3
PTCHD1-AS	NR_073010.2 linkuse as main transcript	n.343+63581T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX53	ENST00000327968.7 linkuse as main transcript	c.400A>G	p.Ile134Val	missense_variant	1/1	6	NM_182699.4	ENSP00000368667.2	Q86TM3
ENSG00000289084	ENST00000687119.1 linkuse as main transcript	n.83-56309T>C		intron_variant
ENSG00000289084	ENST00000687248.1 linkuse as main transcript	n.343+63581T>C		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

112025

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

AN XY:

34189

show subpopulations

Gnomad AFR

AF:

0.0000650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.000373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00420

Gnomad NFE

AF:

0.000357

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.000354

AC:

AN:

183391

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

67835

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000525

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000238

AC:

261

AN:

1098108

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

AN XY:

363468

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000767

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.000296

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000219

Gnomad4 OTH exome

AF:

0.000434

GnomAD4 genome

AF:

0.000277

AC:

AN:

112081

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

AN XY:

34255

show subpopulations

Gnomad4 AFR

AF:

0.0000648

Gnomad4 AMR

AF:

0.000471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.000374

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000357

Gnomad4 OTH

AF:

0.00130

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

DDX53-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 19, 2021

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

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

DDX53: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.050

DANN

Benign

0.53

DEOGEN2

Benign

0.0038

FATHMM_MKL

Benign

0.00036

LIST_S2

Benign

0.15

M_CAP

Benign

0.0011

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PrimateAI

Benign

0.24

PROVEAN

Benign

0.40

REVEL

Benign

0.0090

Sift

Benign

0.68

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.0040

MVP

0.043

MPC

0.075

ClinPred

0.0091

GERP RS

-2.3

Varity_R

0.026

gMVP

0.10

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