Variant chr1-200666422-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001031725.6(DDX59):c.319A>G(p.Ile107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0849 in 1,614,044 control chromosomes in the GnomAD database, including 10,390 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1549 hom., cov: 32)

Exomes 𝑓: 0.081 ( 8841 hom. )

Consequence

DDX59
NM_001031725.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

DDX59 (HGNC:25360): (DEAD-box helicase 59) Predicted to enable RNA binding activity and RNA helicase activity. Predicted to be located in cytoplasm and nucleus. Predicted to be integral component of membrane. Implicated in orofaciodigital syndrome V. [provided by Alliance of Genome Resources, Apr 2022]

DDX59 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046088994).

BP6

Variant 1-200666422-T-C is Benign according to our data. Variant chr1-200666422-T-C is described in ClinVar as [Benign]. Clinvar id is 1530753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX59	NM_001031725.6 linkuse as main transcript	c.319A>G	p.Ile107Val	missense_variant	2/8	ENST00000331314.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX59	ENST00000331314.11 linkuse as main transcript	c.319A>G	p.Ile107Val	missense_variant	2/8	1	NM_001031725.6	P1	Q5T1V6-1
DDX59	ENST00000447706.6 linkuse as main transcript	c.319A>G	p.Ile107Val	missense_variant	2/8	2			Q5T1V6-2
DDX59	ENST00000436897.1 linkuse as main transcript	c.319A>G	p.Ile107Val	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17996

AN:

152060

Hom.:

1547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0535

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.136

AC:

34204

AN:

251350

Hom.:

3723

AF XY:

0.129

AC XY:

17503

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.409

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.0550

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.0815

AC:

119085

AN:

1461866

Hom.:

8841

Cov.:

AF XY:

0.0828

AC XY:

60209

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.247

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.0515

Gnomad4 OTH exome

AF:

0.0991

GnomAD4 genome

AF:

0.118

AC:

18020

AN:

152178

Hom.:

1549

Cov.:

AF XY:

0.126

AC XY:

9386

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0534

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.0745

Hom.:

1373

Bravo

AF:

0.125

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0542

AC:

209

ESP6500AA

AF:

0.145

AC:

639

ESP6500EA

AF:

0.0622

AC:

535

ExAC

AF:

0.129

AC:

15688

Asia WGS

AF:

0.275

AC:

954

AN:

3478

EpiCase

AF:

0.0565

EpiControl

AF:

0.0557

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.4

DANN

Benign

0.79

DEOGEN2

Benign

0.0033

.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.46

T;T;T

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.8

N;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.62

N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0

.;B;.

Vest4

0.017

MPC

0.14

ClinPred

0.0014

GERP RS

4.3

Varity_R

0.056

gMVP

0.089

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