chr17-5450757-C-T

Position:

• chr17-5450757-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020162.4(DHX33):​c.1524+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,610,142 control chromosomes in the GnomAD database, including 27,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2838 hom., cov: 32)
  • Exomes 𝑓: 0.15 (24430 hom.)
• Consequence: DHX33 NM_020162.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949

Genes affected

DHX33 (HGNC:16718): (DEAH-box helicase 33) This gene encodes a member of the DEAD box protein family. The DEAD box proteins are characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX33	NM_020162.4	c.1524+50G>A		intron_variant		ENST00000225296.8	NP_064547.2
DHX33	NM_001199699.2	c.1005+50G>A		intron_variant			NP_001186628.1
DHX33	XM_017024877.2	c.240+50G>A		intron_variant			XP_016880366.1
DHX33	XM_047436418.1	c.1397-351G>A		intron_variant			XP_047292374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX33	ENST00000225296.8	c.1524+50G>A		intron_variant		1	NM_020162.4	ENSP00000225296	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22179 AN: 151924 Hom.: 2844 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.146

GnomAD3 exomes AF: 0.218 AC: 54491 AN: 249538 Hom.: 9207 AF XY: 0.214 AC XY: 28885 AN XY: 134860

Gnomad AFR exome AF: 0.0475

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.642

Gnomad SAS exome AF: 0.306

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.147 AC: 214439 AN: 1458100 Hom.: 24430 Cov.: 31 AF XY: 0.150 AC XY: 109108 AN XY: 725344

Gnomad4 AFR exome AF: 0.0425

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.146 AC: 22186 AN: 152042 Hom.: 2838 Cov.: 32 AF XY: 0.159 AC XY: 11835 AN XY: 74326

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.147

Alfa AF: 0.125 Hom.: 3430

Bravo AF: 0.139

Asia WGS AF: 0.440 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3744714; hg19: chr17-5354077;