Variant X-23001200-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_182699.4(DDX53):c.1143G>T(p.Met381Ile) variant causes a missense change. The variant allele was found at a frequency of 0.124 in 1,209,264 control chromosomes in the GnomAD database, including 7,139 homozygotes. There are 52,794 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.099 ( 527 hom., 3523 hem., cov: 23)

Exomes 𝑓: 0.13 ( 6612 hom. 49271 hem. )

Consequence

DDX53
NM_182699.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.52

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001996249).

BP6

Variant X-23001200-G-T is Benign according to our data. Variant chrX-23001200-G-T is described in ClinVar as [Benign]. Clinvar id is 3055488.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX53	NM_182699.4 linkuse as main transcript	c.1143G>T	p.Met381Ile	missense_variant	1/1	ENST00000327968.7
PTCHD1-AS	NR_073010.2 linkuse as main transcript	n.343+62838C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
DDX53	ENST00000327968.7 linkuse as main transcript	c.1143G>T	p.Met381Ile	missense_variant	1/1	NM_182699.4	P1
	ENST00000687248.1 linkuse as main transcript	n.343+62838C>A		intron_variant, non_coding_transcript_variant
	ENST00000687119.1 linkuse as main transcript	n.83-57052C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

10992

AN:

111476

Hom.:

528

Cov.:

AF XY:

0.104

AC XY:

3516

AN XY:

33672

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.0486

Gnomad AMR

AF:

0.0847

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.339

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.146

AC:

26594

AN:

182773

Hom.:

1453

AF XY:

0.162

AC XY:

10875

AN XY:

67295

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.114

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.127

AC:

139329

AN:

1097733

Hom.:

6612

Cov.:

AF XY:

0.136

AC XY:

49271

AN XY:

363145

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.0979

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.0985

AC:

10988

AN:

111531

Hom.:

527

Cov.:

AF XY:

0.104

AC XY:

3523

AN XY:

33737

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.0846

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.256

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.121

Hom.:

10075

Bravo

AF:

0.0860

TwinsUK

AF:

0.104

AC:

387

ALSPAC

AF:

0.116

AC:

336

ESP6500AA

AF:

0.0175

AC:

ESP6500EA

AF:

0.117

AC:

789

ExAC

AF:

0.149

AC:

18142

EpiCase

AF:

0.113

EpiControl

AF:

0.116

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DDX53-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.11

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.000038

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.15

MutPred

0.26

Gain of methylation at K380 (P = 0.0255);

MPC

0.51

ClinPred

0.024

GERP RS

4.3

Varity_R

0.98

gMVP

0.67

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