rs3795634

Positions:

• chr1-200666422-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.75

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	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	c.319A>G	p.Ile107Val	missense_variant	2/8	1	NM_001031725.6	P1
DDX59	ENST00000447706.6	c.319A>G	p.Ile107Val	missense_variant	2/8	2
DDX59	ENST00000436897.1	c.319A>G	p.Ile107Val	missense_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17996 AN: 152060 Hom.: 1547 Cov.: 32

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

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.: 31 AF XY: 0.0828 AC XY: 60209 AN XY: 727232

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.: 32 AF XY: 0.126 AC XY: 9386 AN XY: 74384

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

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	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.4
DANN	Benign	0.79
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.46	T;T;T
MetaRNN	Benign	0.0046	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.8	N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.61	T
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	T
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

Other links and lift over

dbSNP: rs3795634; hg19: chr1-200635550; COSMIC: COSV58750950; COSMIC: COSV58750950;