17-5468939-G-A

Variant names:

• chr17-5468939-G-A
• rs28372907
• NM_020162.4:c.-80C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

DHX33-DT (HGNC:52937): (DHX33 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020162.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX33	NM_020162.4	MANE Select	c.-80C>T		5_prime_UTR	Exon 1 of 12	NP_064547.2
	DHX33	NM_001199699.2		c.-438C>T		5_prime_UTR	Exon 1 of 11	NP_001186628.1	Q9H6R0-2
	DHX33-DT	NR_135644.1		n.-153G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX33	ENST00000225296.8	TSL:1 MANE Select	c.-80C>T		5_prime_UTR	Exon 1 of 12	ENSP00000225296.3	Q9H6R0-1
	DHX33-DT	ENST00000826977.1		n.307+595G>A		intron	N/A
	DHX33-DT	ENST00000826978.1		n.60+624G>A		intron	N/A

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

GnomAD2 exomes AF: 0.237 AC: 26366 AN: 111224 AF XY: 0.243

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 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

African (AFR) AF: 0.524 AC: 14233 AN: 27158

American (AMR) AF: 0.139 AC: 4447 AN: 32092

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 4647 AN: 23604

East Asian (EAS) AF: 0.351 AC: 11530 AN: 32870

South Asian (SAS) AF: 0.287 AC: 21722 AN: 75560

European-Finnish (FIN) AF: 0.227 AC: 9025 AN: 39694

Middle Eastern (MID) AF: 0.229 AC: 909 AN: 3970

European-Non Finnish (NFE) AF: 0.195 AC: 192323 AN: 987582

Other (OTH) AF: 0.233 AC: 12502 AN: 53746

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

African (AFR) AF: 0.499 AC: 20683 AN: 41440

American (AMR) AF: 0.181 AC: 2773 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1657 AN: 5130

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4824

European-Finnish (FIN) AF: 0.228 AC: 2410 AN: 10560

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13510 AN: 67938

Other (OTH) AF: 0.244 AC: 516 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		1.3
PromoterAI		0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28372907; hg19: chr17-5372259; COSMIC: COSV107235288; COSMIC: COSV107235288;