Variant chrX-23000242-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_182699.4(DDX53):c.185T>C(p.Val62Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,186,662 control chromosomes in the GnomAD database, including 825 homozygotes. There are 3,507 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.055 ( 409 hom., 1644 hem., cov: 24)

Exomes 𝑓: 0.0065 ( 416 hom. 1863 hem. )

Consequence

DDX53
NM_182699.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.862

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020723045).

BP6

Variant X-23000242-T-C is Benign according to our data. Variant chrX-23000242-T-C is described in ClinVar as [Benign]. Clinvar id is 3055405.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX53	NM_182699.4 linkuse as main transcript	c.185T>C	p.Val62Ala	missense_variant	1/1	ENST00000327968.7	NP_874358.2	Q86TM3
PTCHD1-AS	NR_073010.2 linkuse as main transcript	n.343+63796A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX53	ENST00000327968.7 linkuse as main transcript	c.185T>C	p.Val62Ala	missense_variant	1/1	6	NM_182699.4	ENSP00000368667.2	Q86TM3
ENSG00000289084	ENST00000687119.1 linkuse as main transcript	n.83-56094A>G		intron_variant
ENSG00000289084	ENST00000687248.1 linkuse as main transcript	n.343+63796A>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

6095

AN:

112006

Hom.:

407

Cov.:

AF XY:

0.0477

AC XY:

1634

AN XY:

34228

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.00188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0335

Gnomad NFE

AF:

0.000751

Gnomad OTH

AF:

0.0463

GnomAD3 exomes

AF:

0.0184

AC:

2993

AN:

162380

Hom.:

223

AF XY:

0.0132

AC XY:

684

AN XY:

51900

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.0000772

Gnomad SAS exome

AF:

0.000594

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000830

Gnomad OTH exome

AF:

0.00899

GnomAD4 exome

AF:

0.00646

AC:

6946

AN:

1074602

Hom.:

416

Cov.:

AF XY:

0.00538

AC XY:

1863

AN XY:

346128

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.00105

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000688

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000491

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0546

AC:

6115

AN:

112060

Hom.:

409

Cov.:

AF XY:

0.0479

AC XY:

1644

AN XY:

34292

show subpopulations

Gnomad4 AFR

AF:

0.186

Gnomad4 AMR

AF:

0.0266

Gnomad4 ASJ

AF:

0.00188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00147

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000733

Gnomad4 OTH

AF:

0.0470

Alfa

AF:

0.00707

Hom.:

418

Bravo

AF:

0.0642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.187

AC:

719

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.0180

AC:

2177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.97

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0070

DANN

Benign

0.53

DEOGEN2

Benign

0.0032

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.42

PrimateAI

Benign

0.43

PROVEAN

Benign

1.8

REVEL

Benign

0.027

Sift

Benign

0.48

Sift4G

Benign

0.82

Polyphen

0.0010

Vest4

0.016

MPC

0.11

ClinPred

0.0055

GERP RS

-4.1

Varity_R

0.021

gMVP

0.36

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