rs1140409

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004396.5(DDX5):c.1438T>G(p.Ser480Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 1,612,270 control chromosomes in the GnomAD database, including 3,143 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.050 ( 264 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2879 hom. )

Consequence

DDX5
NM_004396.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

Publications

25 publications found

Variant links:

Genes affected

DDX5 (HGNC:2746): (DEAD-box helicase 5) This gene encodes a member of the DEAD box family of RNA helicases that are involved in a variety of cellular processes as a result of its role as an adaptor molecule, promoting interactions with a large number of other factors. This protein is involved in pathways that include the alteration of RNA structures, plays a role as a coregulator of transcription, a regulator of splicing, and in the processing of small noncoding RNAs. Members of this family contain nine conserved motifs, including the conserved Asp-Glu-Ala-Asp (DEAD) motif, important to ATP binding and hydrolysis as well as RNA binding and unwinding activities. Dysregulation of this gene may play a role in cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2017]

DDX5 links:

MIR3064 (HGNC:41652): (microRNA 3064) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3064 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014832616).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX5	NM_004396.5 link	c.1438T>G	p.Ser480Ala	missense_variant	Exon 12 of 13	ENST00000225792.10	NP_004387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX5	ENST00000225792.10 link	c.1438T>G	p.Ser480Ala	missense_variant	Exon 12 of 13	1	NM_004396.5	ENSP00000225792.5

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7587

AN:

152220

Hom.:

264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0879

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0341

Gnomad FIN

AF:

0.0942

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0709

Gnomad OTH

AF:

0.0545

GnomAD2 exomes

AF:

0.0540

AC:

13463

AN:

249176

AF XY:

0.0558

show subpopulations

Gnomad AFR exome

AF:

0.00961

Gnomad AMR exome

AF:

0.0260

Gnomad ASJ exome

AF:

0.0874

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0866

Gnomad NFE exome

AF:

0.0732

Gnomad OTH exome

AF:

0.0671

GnomAD4 exome

AF:

0.0599

AC:

87467

AN:

1459932

Hom.:

2879

Cov.:

AF XY:

0.0601

AC XY:

43645

AN XY:

726208

show subpopulations

African (AFR)

AF:

0.00926

AC:

310

AN:

33460

American (AMR)

AF:

0.0271

AC:

1211

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.0869

AC:

2263

AN:

26056

East Asian (EAS)

AF:

0.000126

AC:

AN:

39688

South Asian (SAS)

AF:

0.0355

AC:

3050

AN:

86012

European-Finnish (FIN)

AF:

0.0882

AC:

4704

AN:

53348

Middle Eastern (MID)

AF:

0.0731

AC:

421

AN:

5762

European-Non Finnish (NFE)

AF:

0.0648

AC:

72003

AN:

1110650

Other (OTH)

AF:

0.0580

AC:

3500

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

4051

8102

12152

16203

20254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2544

5088

7632

10176

12720

<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:

0.0498

AC:

7584

AN:

152338

Hom.:

264

Cov.:

AF XY:

0.0505

AC XY:

3760

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0102

AC:

425

AN:

41584

American (AMR)

AF:

0.0409

AC:

626

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0879

AC:

305

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.0344

AC:

166

AN:

4830

European-Finnish (FIN)

AF:

0.0942

AC:

1000

AN:

10620

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0709

AC:

4822

AN:

68018

Other (OTH)

AF:

0.0539

AC:

114

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

378

755

1133

1510

1888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0622

Hom.:

1047

Bravo

AF:

0.0429

TwinsUK

AF:

0.0564

AC:

209

ALSPAC

AF:

0.0589

AC:

227

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0715

AC:

615

ExAC

AF:

0.0561

AC:

6815

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.089

T;.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.

PhyloP100

3.5

PrimateAI

Uncertain

0.54

REVEL

Benign

0.17

Sift4G

Benign

0.21

T;T;T

Polyphen

0.024

B;.;.

Vest4

0.080

ClinPred

0.014

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.096

gMVP

0.29

Mutation Taster

=98/2

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

Computational scores

Splicing

Publications

Other links and lift over