rs28372907

Positions:

• chr17-5468939-G-A
• chr17-5468939-G-C

Variant summary

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

The NM_020162.4(DHX33):​c.-80C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,428,252 control chromosomes in the GnomAD database, including 39,530 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 0.29 (7773 hom., cov: 32)
  • Exomes 𝑓: 0.21 (31757 hom.)
• Consequence: DHX33 NM_020162.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX33	NM_020162.4	c.-80C>T		5_prime_UTR_variant	1/12	ENST00000225296.8	NP_064547.2
DHX33	NM_001199699.2	c.-438C>T		5_prime_UTR_variant	1/11		NP_001186628.1
DHX33	XM_047436418.1	c.-80C>T		5_prime_UTR_variant	1/9		XP_047292374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX33	ENST00000225296.8	c.-80C>T		5_prime_UTR_variant	1/12	1	NM_020162.4	ENSP00000225296.3
DHX33	ENST00000433302.7	c.-80C>T		upstream_gene_variant		1		ENSP00000413779.3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43821 AN: 151858 Hom.: 7716 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.238

GnomAD3 exomes AF: 0.237 AC: 26366 AN: 111224 Hom.: 3441 AF XY: 0.243 AC XY: 15134 AN XY: 62202

Gnomad AFR exome AF: 0.561

Gnomad AMR exome AF: 0.136

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.357

Gnomad SAS exome AF: 0.292

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.213 AC: 271338 AN: 1276276 Hom.: 31757 Cov.: 19 AF XY: 0.215 AC XY: 136396 AN XY: 634814

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.289 AC: 43935 AN: 151976 Hom.: 7773 Cov.: 32 AF XY: 0.289 AC XY: 21474 AN XY: 74292

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.244

Alfa AF: 0.228 Hom.: 869

Bravo AF: 0.295

Asia WGS AF: 0.334 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs28372907; hg19: chr17-5372259;