Variant chrX-23000422-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_182699.4(DDX53):c.365A>C(p.Glu122Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,450 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000064 ( 0 hom. 3 hem. )

Consequence

DDX53
NM_182699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.119

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06992355).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX53	NM_182699.4 linkuse as main transcript	c.365A>C	p.Glu122Ala	missense_variant	1/1	ENST00000327968.7	NP_874358.2	Q86TM3
PTCHD1-AS	NR_073010.2 linkuse as main transcript	n.343+63616T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX53	ENST00000327968.7 linkuse as main transcript	c.365A>C	p.Glu122Ala	missense_variant	1/1	6	NM_182699.4	ENSP00000368667.2	Q86TM3
ENSG00000289084	ENST00000687119.1 linkuse as main transcript	n.83-56274T>G		intron_variant
ENSG00000289084	ENST00000687248.1 linkuse as main transcript	n.343+63616T>G		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000275

AC:

AN:

181757

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66279

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000614

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097450

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362852

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.365A>C (p.E122A) alteration is located in exon 1 (coding exon 1) of the DDX53 gene. This alteration results from a A to C substitution at nucleotide position 365, causing the glutamic acid (E) at amino acid position 122 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.3

DANN

Benign

0.91

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.44

M_CAP

Benign

0.0027

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.022

Sift

Benign

0.20

Sift4G

Benign

0.56

Polyphen

0.21

Vest4

0.085

MutPred

0.15

Gain of MoRF binding (P = 0.0792);

MVP

0.068

MPC

0.098

ClinPred

0.18

GERP RS

0.50

Varity_R

0.11

gMVP

0.19

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