dbSNP rs369128752: DDX43:p.Gly49Ala (chr6-73395051-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018665.3(DDX43):c.146G>C(p.Gly49Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

DDX43
NM_018665.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

Publications

0 publications found

Variant links:

Genes affected

DDX43 (HGNC:18677): (DEAD-box helicase 43) The protein encoded by this gene is an ATP-dependent RNA helicase in the DEAD-box family and displays tumor-specific expression. [provided by RefSeq, Jul 2008]

DDX43 links:

OOEP (HGNC:21382): (oocyte expressed protein) Predicted to enable RNA binding activity. Predicted to be involved in several processes, including cytoskeleton organization; positive regulation of double-strand break repair via homologous recombination; and positive regulation of meiotic nuclear division. Predicted to act upstream of or within several processes, including embryo implantation; in utero embryonic development; and protein phosphorylation. Located in cytoplasm and nucleus. Part of subcortical maternal complex. [provided by Alliance of Genome Resources, Apr 2022]

OOEP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08065963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018665.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX43	NM_018665.3	MANE Select	c.146G>C	p.Gly49Ala	missense	Exon 1 of 17	NP_061135.2	Q9NXZ2-1
OOEP	NM_001428256.1		c.-681C>G		5_prime_UTR	Exon 1 of 3	NP_001415185.1	F2Z364
OOEP	NR_190285.1		n.113C>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX43	ENST00000370336.5	TSL:1 MANE Select	c.146G>C	p.Gly49Ala	missense	Exon 1 of 17	ENSP00000359361.4	Q9NXZ2-1
OOEP	ENST00000370363.5	TSL:1	c.-451C>G		5_prime_UTR	Exon 1 of 4	ENSP00000359388.1	F2Z364
DDX43	ENST00000942801.1		c.146G>C	p.Gly49Ala	missense	Exon 1 of 16	ENSP00000612860.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251182

AF XY:

0.00000736

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions as Germline

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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.034

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.36

M_CAP

Benign

0.0046

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

1.2

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.3

REVEL

Benign

0.092

Sift

Benign

0.24

Sift4G

Benign

0.11

Polyphen

0.0020

Vest4

0.11

MVP

0.37

MPC

0.37

ClinPred

0.065

GERP RS

3.8

PromoterAI

0.0059

Neutral

(source)

Varity_R

0.11

gMVP

0.17

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over