chrX-23000137-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_182699.4(DDX53):c.80G>A(p.Ser27Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000078 in 1,192,138 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000080 ( 0 hom. 18 hem. )

Consequence

DDX53
NM_182699.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.598

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06800479).

BP6

Variant X-23000137-G-A is Benign according to our data. Variant chrX-23000137-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2516544.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX53	NM_182699.4 link	c.80G>A	p.Ser27Asn	missense_variant	Exon 1 of 1	ENST00000327968.7	NP_874358.2	Q86TM3
PTCHD1-AS	NR_073010.2 link	n.343+63901C>T		intron_variant	Intron 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DDX53	ENST00000327968.7 link	c.80G>A	p.Ser27Asn	missense_variant	Exon 1 of 1	6	NM_182699.4	ENSP00000368667.2	Q86TM3
PTCHD1-AS	ENST00000687119.1 link	n.83-55989C>T		intron_variant	Intron 1 of 3
PTCHD1-AS	ENST00000687248.2 link	n.371+63901C>T		intron_variant	Intron 3 of 8

Frequencies

GnomAD3 genomes

AF:

0.0000623

AC:

AN:

112285

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

165364

AF XY:

0.0000189

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000796

AC:

AN:

1079853

Hom.:

Cov.:

AF XY:

0.0000514

AC XY:

AN XY:

349897

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25814

American (AMR)

AF:

0.00

AC:

AN:

33057

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18517

East Asian (EAS)

AF:

0.00

AC:

AN:

29872

South Asian (SAS)

AF:

0.00

AC:

AN:

50716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3915

European-Non Finnish (NFE)

AF:

0.0000973

AC:

AN:

832646

Other (OTH)

AF:

0.000111

AC:

AN:

45152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000623

AC:

AN:

112285

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34441

show subpopulations

African (AFR)

AF:

0.000130

AC:

AN:

30876

American (AMR)

AF:

0.00

AC:

AN:

10630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2660

East Asian (EAS)

AF:

0.00

AC:

AN:

3555

South Asian (SAS)

AF:

0.00

AC:

AN:

2717

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000563

AC:

AN:

53286

Other (OTH)

AF:

0.00

AC:

AN:

1502

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 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:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 12, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.80G>A (p.S27N) alteration is located in exon 1 (coding exon 1) of the DDX53 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the serine (S) at amino acid position 27 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DDX53: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0096

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.22

M_CAP

Benign

0.012

MetaRNN

Benign

0.068

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.60

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.30

REVEL

Benign

0.042

Sift

Benign

0.12

Sift4G

Benign

0.55

Polyphen

0.17

Vest4

0.077

MVP

0.082

MPC

0.12

ClinPred

0.042

GERP RS

3.0

PromoterAI

0.011

Neutral

(source)

Varity_R

0.094

gMVP

0.16

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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