Variant chr1-200648497-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001031725.6(DDX59):c.1538G>A(p.Ser513Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,614,166 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 16 hom. )

Consequence

DDX59
NM_001031725.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.31

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063795447).

BP6

Variant 1-200648497-C-T is Benign according to our data. Variant chr1-200648497-C-T is described in ClinVar as [Benign]. Clinvar id is 728607.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00219 (333/152324) while in subpopulation EAS AF= 0.00347 (18/5190). AF 95% confidence interval is 0.00224. There are 7 homozygotes in gnomad4. There are 241 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX59	NM_001031725.6 linkuse as main transcript	c.1538G>A	p.Ser513Asn	missense_variant	7/8	ENST00000331314.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX59	ENST00000331314.11 linkuse as main transcript	c.1538G>A	p.Ser513Asn	missense_variant	7/8	1	NM_001031725.6	P1	Q5T1V6-1

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00264

AC:

663

AN:

251426

Hom.:

AF XY:

0.00250

AC XY:

340

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00185

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.0221

Gnomad NFE exome

AF:

0.000800

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00121

AC:

1772

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

873

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00302

Gnomad4 EAS exome

AF:

0.00436

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.0191

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00219

AC:

333

AN:

152324

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0253

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000681

Hom.:

Bravo

AF:

0.000382

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00226

AC:

274

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

- -

DDX59-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.35

DEOGEN2

Benign

0.052

.;.;T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0064

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.3

N;.;N;.

MutationTaster

Benign

0.77

N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

1.6

N;N;N;N

REVEL

Benign

0.093

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.0

.;.;B;.

Vest4

0.17

MVP

0.68

MPC

0.16

ClinPred

0.017

GERP RS

2.2

Varity_R

0.032

gMVP

0.22

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