1-200648405-G-T

Position:

• chr1-200648405-G-T

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.1596+34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,607,978 control chromosomes in the GnomAD database, including 15,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1080 hom., cov: 31)
  • Exomes 𝑓: 0.13 (14356 hom.)
• Consequence: DDX59 NM_001031725.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.813

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 (BayesDel_noAF=-0.91).
• BP6: Variant 1-200648405-G-T is Benign according to our data. Variant chr1-200648405-G-T is described in ClinVar as [Benign]. Clinvar id is 1269466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX59	NM_001031725.6	c.1596+34C>A		intron_variant		ENST00000331314.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX59	ENST00000331314.11	c.1596+34C>A		intron_variant		1	NM_001031725.6	P1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15269 AN: 151950 Hom.: 1080 Cov.: 31

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.103 AC: 25592 AN: 247414 Hom.: 1736 AF XY: 0.104 AC XY: 13855 AN XY: 133850

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0345

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.134 AC: 195130 AN: 1455912 Hom.: 14356 Cov.: 31 AF XY: 0.131 AC XY: 94953 AN XY: 724154

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.0683

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0356

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.100 AC: 15266 AN: 152066 Hom.: 1080 Cov.: 31 AF XY: 0.0972 AC XY: 7224 AN XY: 74326

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0913

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.109

Alfa AF: 0.135 Hom.: 995

Bravo AF: 0.0962

Asia WGS AF: 0.0200 AC: 72 AN: 3478

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

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.073
DANN	Benign	0.78

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: rs17416794; hg19: chr1-200617533;