Variant 1-111755959-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007204.5(DDX20):c.35C>T(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000583 in 1,591,826 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

DDX20
NM_007204.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.686

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027470171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX20	NM_007204.5 linkuse as main transcript	c.35C>T	p.Ala12Val	missense_variant	1/11	ENST00000369702.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX20	ENST00000369702.5 linkuse as main transcript	c.35C>T	p.Ala12Val	missense_variant	1/11	1	NM_007204.5	P2	Q9UHI6-1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000867

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

235342

Hom.:

AF XY:

0.000194

AC XY:

AN XY:

128746

show subpopulations

Gnomad AFR exome

AF:

0.0000706

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000415

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.000602

AC:

866

AN:

1439462

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

412

AN XY:

712386

show subpopulations

Gnomad4 AFR exome

AF:

0.0000607

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000716

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.000407

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0000721

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:

0.000867

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000527

Hom.:

Bravo

AF:

0.000336

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000584

AC:

ExAC

AF:

0.000215

AC:

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

Nov 19, 2022

The c.35C>T (p.A12V) alteration is located in exon 1 (coding exon 1) of the DDX20 gene. This alteration results from a C to T substitution at nucleotide position 35, causing the alanine (A) at amino acid position 12 to be replaced by a valine (V). 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

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.066

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0082

LIST_S2

Benign

0.53

M_CAP

Benign

0.043

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.28

REVEL

Benign

0.019

Sift

Benign

0.26

Sift4G

Benign

0.11

Polyphen

0.041

Vest4

0.12

MVP

0.56

MPC

0.078

ClinPred

0.021

GERP RS

1.2

Varity_R

0.034

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over