dbSNP rs143131443: DDX53:p.Glu164Lys (chrX-23000547-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

1 publications found

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:

PTCHD1-AS (HGNC:37703): (PTCHD1 antisense RNA (head to head))

PTCHD1-AS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 717072.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 27 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX53	NM_182699.4 link	c.490G>A	p.Glu164Lys	missense_variant	Exon 1 of 1	ENST00000327968.7	NP_874358.2	Q86TM3
PTCHD1-AS	NR_073010.2 link	n.343+63491C>T		intron_variant	Intron 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DDX53	ENST00000327968.7 link	c.490G>A	p.Glu164Lys	missense_variant	Exon 1 of 1	6	NM_182699.4	ENSP00000368667.2	Q86TM3
PTCHD1-AS	ENST00000687119.1 link	n.83-56399C>T		intron_variant	Intron 1 of 3
PTCHD1-AS	ENST00000687248.2 link	n.371+63491C>T		intron_variant	Intron 3 of 8

Frequencies

GnomAD3 genomes

AF:

0.000817

AC:

AN:

111410

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000642

AC:

117

AN:

182349

AF XY:

0.000583

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 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

African (AFR)

AF:

0.000189

AC:

AN:

26389

American (AMR)

AF:

0.000114

AC:

AN:

35140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19360

East Asian (EAS)

AF:

0.00

AC:

AN:

30192

South Asian (SAS)

AF:

0.0000185

AC:

AN:

53948

European-Finnish (FIN)

AF:

0.000987

AC:

AN:

40519

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00153

AC:

1292

AN:

841944

Other (OTH)

AF:

0.00132

AC:

AN:

46077

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

119

178

238

297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000807

AC:

AN:

111465

Hom.:

Cov.:

AF XY:

0.000800

AC XY:

AN XY:

33757

show subpopulations

African (AFR)

AF:

0.000196

AC:

AN:

30610

American (AMR)

AF:

0.000190

AC:

AN:

10531

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3523

South Asian (SAS)

AF:

0.00

AC:

AN:

2668

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

6029

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00141

AC:

AN:

53050

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00112

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

Jul 30, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

0.054

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over