Variant 1-200649110-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001031725.6(DDX59):c.1431A>G(p.Ser477Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,566,354 control chromosomes in the GnomAD database, including 726,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69311 hom., cov: 32)

Exomes 𝑓: 0.96 ( 657170 hom. )

Consequence

DDX59
NM_001031725.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.22

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-200649110-T-C is Benign according to our data. Variant chr1-200649110-T-C is described in ClinVar as [Benign]. Clinvar id is 1255474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX59	NM_001031725.6 linkuse as main transcript	c.1431A>G	p.Ser477Ser	synonymous_variant	6/8	ENST00000331314.11	NP_001026895.2	Q5T1V6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX59	ENST00000331314.11 linkuse as main transcript	c.1431A>G	p.Ser477Ser	synonymous_variant	6/8	1	NM_001031725.6	ENSP00000330460.6		Q5T1V6-1

Frequencies

GnomAD3 genomes

AF:

0.954

AC:

145122

AN:

152138

Hom.:

69257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.925

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.957

Gnomad ASJ

AF:

0.957

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.982

Gnomad FIN

AF:

0.991

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.959

Gnomad OTH

AF:

0.958

GnomAD3 exomes

AF:

0.967

AC:

205431

AN:

212522

Hom.:

99321

AF XY:

0.967

AC XY:

112461

AN XY:

116288

show subpopulations

Gnomad AFR exome

AF:

0.922

Gnomad AMR exome

AF:

0.973

Gnomad ASJ exome

AF:

0.959

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.978

Gnomad FIN exome

AF:

0.988

Gnomad NFE exome

AF:

0.961

Gnomad OTH exome

AF:

0.965

GnomAD4 exome

AF:

0.964

AC:

1363194

AN:

1414098

Hom.:

657170

Cov.:

AF XY:

0.964

AC XY:

677754

AN XY:

702782

show subpopulations

Gnomad4 AFR exome

AF:

0.923

Gnomad4 AMR exome

AF:

0.973

Gnomad4 ASJ exome

AF:

0.959

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.978

Gnomad4 FIN exome

AF:

0.988

Gnomad4 NFE exome

AF:

0.962

Gnomad4 OTH exome

AF:

0.964

GnomAD4 genome

AF:

0.954

AC:

145234

AN:

152256

Hom.:

69311

Cov.:

AF XY:

0.957

AC XY:

71256

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.925

Gnomad4 AMR

AF:

0.957

Gnomad4 ASJ

AF:

0.957

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.982

Gnomad4 FIN

AF:

0.991

Gnomad4 NFE

AF:

0.959

Gnomad4 OTH

AF:

0.959

Alfa

AF:

0.957

Hom.:

110159

Bravo

AF:

0.951

Asia WGS

AF:

0.983

AC:

3417

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Orofaciodigital syndrome V

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.041

DANN

Benign

0.44

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