Variant 5-55790582-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_024415.3(DDX4):c.1179T>G(p.Cys393Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000296 in 1,589,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

DDX4
NM_024415.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

DDX4 (HGNC:18700): (DEAD-box helicase 4) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a homolog of VASA proteins in Drosophila and several other species. The gene is specifically expressed in the germ cell lineage in both sexes and functions in germ cell development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

DDX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.784

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX4	NM_024415.3 linkuse as main transcript	c.1179T>G	p.Cys393Trp	missense_variant	16/22	ENST00000505374.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX4	ENST00000505374.6 linkuse as main transcript	c.1179T>G	p.Cys393Trp	missense_variant	16/22	1	NM_024415.3	P1	Q9NQI0-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

249440

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

134818

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:

0.000167

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000292

AC:

AN:

1437336

Hom.:

Cov.:

AF XY:

0.0000321

AC XY:

AN XY:

716736

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:

0.000153

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000220

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000302

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 12, 2022

The c.1179T>G (p.C393W) alteration is located in exon 16 (coding exon 15) of the DDX4 gene. This alteration results from a T to G substitution at nucleotide position 1179, causing the cysteine (C) at amino acid position 393 to be replaced by a tryptophan (W). 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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

D;D;D;D;.;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.78

D;D;D;D;D;D

MetaSVM

Benign

-0.76

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.7

D;D;D;D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.036

D;T;T;D;T;T

Sift4G

Uncertain

0.0040

D;D;D;D;D;T

Polyphen

1.0, 1.0

.;D;D;.;D;.

Vest4

0.79

MVP

0.11

MPC

0.72

ClinPred

0.90

GERP RS

4.7

Varity_R

0.67

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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