dbSNP rs197412: DDX20:p.Ile636Thr (chr1-111766331-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007204.5(DDX20):c.1907T>C(p.Ile636Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,432 control chromosomes in the GnomAD database, including 139,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.48 ( 18790 hom., cov: 32)

Exomes 𝑓: 0.40 ( 121035 hom. )

Consequence

DDX20
NM_007204.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

DDX20 (HGNC:2743): (DEAD-box helicase 20) 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 has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

DDX20 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.599391E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX20	NM_007204.5 link	c.1907T>C	p.Ile636Thr	missense_variant	Exon 11 of 11	ENST00000369702.5	NP_009135.4	Q9UHI6-1Q9H4N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX20	ENST00000369702.5 link	c.1907T>C	p.Ile636Thr	missense_variant	Exon 11 of 11	1	NM_007204.5	ENSP00000358716.4		Q9UHI6-1

Frequencies

GnomAD3 genomes

AF:

0.480

AC:

72961

AN:

151948

Hom.:

18749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.461

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.475

GnomAD3 exomes

AF:

0.426

AC:

106929

AN:

250918

Hom.:

23831

AF XY:

0.413

AC XY:

56028

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.530

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.402

AC:

587222

AN:

1461366

Hom.:

121035

Cov.:

AF XY:

0.399

AC XY:

289877

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.698

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.356

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.463

Gnomad4 NFE exome

AF:

0.393

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.481

AC:

73068

AN:

152066

Hom.:

18790

Cov.:

AF XY:

0.477

AC XY:

35466

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.682

Gnomad4 AMR

AF:

0.462

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.448

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.473

Alfa

AF:

0.409

Hom.:

25500

Bravo

AF:

0.492

TwinsUK

AF:

0.393

AC:

1456

ALSPAC

AF:

0.388

AC:

1497

ESP6500AA

AF:

0.670

AC:

2950

ESP6500EA

AF:

0.389

AC:

3345

ExAC

AF:

0.427

AC:

51820

Asia WGS

AF:

0.349

AC:

1219

AN:

3478

EpiCase

AF:

0.394

EpiControl

AF:

0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.045

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.092

T;T

MetaRNN

Benign

0.0000026

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.8

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.12

Sift

Benign

0.65

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.0

B;B

Vest4

0.035

MPC

0.10

ClinPred

0.0037

GERP RS

3.9

Varity_R

0.013

gMVP

0.074

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over