17-5468939-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020162.4(DHX33):​c.-80C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000235 in 1,278,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: DHX33 NM_020162.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX33	NM_020162.4	c.-80C>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000225296.8	NP_064547.2
DHX33	NM_001199699.2	c.-438C>A		5_prime_UTR_variant	Exon 1 of 11		NP_001186628.1
DHX33	XM_047436418.1	c.-80C>A		5_prime_UTR_variant	Exon 1 of 9		XP_047292374.1
DHX33-DT	NR_135644.1	n.-153G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX33	ENST00000225296.8	c.-80C>A		5_prime_UTR_variant	Exon 1 of 12	1	NM_020162.4	ENSP00000225296.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000235 AC: 3 AN: 1278068 Hom.: 0 Cov.: 19 AF XY: 0.00000315 AC XY: 2 AN XY: 635622

African (AFR) AF: 0.00 AC: 0 AN: 27232

American (AMR) AF: 0.00 AC: 0 AN: 32112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23632

East Asian (EAS) AF: 0.00 AC: 0 AN: 32900

South Asian (SAS) AF: 0.0000265 AC: 2 AN: 75614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3976

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 989072

Other (OTH) AF: 0.00 AC: 0 AN: 53818

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.79
PhyloP100		1.3
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs28372907; hg19: chr17-5372259;