Genetic Variant NM_004939.3:c.13T>A (chr2-15591946-T-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004939.3(DDX1):c.13T>A(p.Ser5Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,433,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

DDX1
NM_004939.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Publications

0 publications found

Variant links:

Genes affected

DDX1 (HGNC:2734): (DEAD-box helicase 1) 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 that acts as an ATP-dependent RNA helicase that has been found to promote coronaviruses replication. [provided by RefSeq, Aug 2021]

DDX1 links:

ENSG00000302930 (HGNC:):

ENSG00000302930 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21127707).

BS2

High AC in GnomAdExome4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004939.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX1	NM_004939.3	MANE Select	c.13T>A	p.Ser5Thr	missense	Exon 1 of 26	NP_004930.1	Q92499-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX1	ENST00000233084.8	TSL:1 MANE Select	c.13T>A	p.Ser5Thr	missense	Exon 1 of 26	ENSP00000233084.3	Q92499-1
DDX1	ENST00000617198.5	TSL:1	c.-148T>A		5_prime_UTR	Exon 1 of 24	ENSP00000482416.2	A0A087WZ71
DDX1	ENST00000381341.7	TSL:5	c.13T>A	p.Ser5Thr	missense	Exon 2 of 27	ENSP00000370745.1	Q92499-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152146

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1281530

Hom.:

Cov.:

AF XY:

0.0000176

AC XY:

AN XY:

624770

show subpopulations

African (AFR)

AF:

0.0000402

AC:

AN:

24846

American (AMR)

AF:

0.00

AC:

AN:

18256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18728

East Asian (EAS)

AF:

0.00

AC:

AN:

28110

South Asian (SAS)

AF:

0.00

AC:

AN:

63330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5196

European-Non Finnish (NFE)

AF:

0.0000205

AC:

AN:

1024486

Other (OTH)

AF:

0.00

AC:

AN:

52526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000197

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.14

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.056

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

PhyloP100

3.9

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.98

REVEL

Benign

0.064

Sift

Benign

0.063

Sift4G

Benign

0.067

Polyphen

0.0

Vest4

0.35

MutPred

0.23

Loss of glycosylation at S5 (P = 0.0429)

MVP

0.48

MPC

0.24

ClinPred

0.53

GERP RS

4.7

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

4.0

Varity_R

0.17

gMVP

0.36

Mutation Taster

=84/16

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over