22-38488770-C-T

Variant names:

• chr22-38488770-C-T
• rs5750609
• NM_006386.5:c.1448-655G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006386.5(DDX17):​c.1448-655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 985,428 control chromosomes in the GnomAD database, including 6,335 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 0.090 (828 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5507 hom.)
• Consequence: DDX17 NM_006386.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 14 publications found

Genes affected

DDX17 (HGNC:2740): (DEAD-box helicase 17) DEAD box proteins, 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 splicesosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an ATPase activated by a variety of RNA species, but not by dsDNA. This protein, and that encoded by DDX5 gene, are more closely related to each other than to any other member of the DEAD box family. This gene can encode multiple isoforms due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) start codon. [provided by RefSeq, Apr 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006386.5. 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
	DDX17	NM_006386.5	MANE Select	c.1448-655G>A		intron	N/A	NP_006377.2
	DDX17	NM_001098504.2		c.1448-655G>A		intron	N/A	NP_001091974.1	A0A5H1ZRQ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX17	ENST00000403230.3	TSL:1 MANE Select	c.1448-655G>A		intron	N/A	ENSP00000385536.2	Q92841-4
	DDX17	ENST00000396821.8	TSL:1	c.1448-655G>A		intron	N/A	ENSP00000380033.4	A0A5H1ZRQ2
	DDX17	ENST00000216019.11	TSL:1	n.4790G>A		non_coding_transcript_exon	Exon 11 of 12

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13727 AN: 152112 Hom.: 830 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.0674

Gnomad ASJ AF: 0.0901

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0913

GnomAD4 exome AF: 0.113 AC: 94111 AN: 833196 Hom.: 5507 Cov.: 30 AF XY: 0.113 AC XY: 43307 AN XY: 384770

African (AFR) AF: 0.0139 AC: 219 AN: 15790

American (AMR) AF: 0.0656 AC: 67 AN: 1022

Ashkenazi Jewish (ASJ) AF: 0.0938 AC: 483 AN: 5148

East Asian (EAS) AF: 0.162 AC: 588 AN: 3634

South Asian (SAS) AF: 0.126 AC: 2076 AN: 16470

European-Finnish (FIN) AF: 0.175 AC: 48 AN: 274

Middle Eastern (MID) AF: 0.119 AC: 193 AN: 1620

European-Non Finnish (NFE) AF: 0.115 AC: 87519 AN: 761944

Other (OTH) AF: 0.107 AC: 2918 AN: 27294

GnomAD4 genome AF: 0.0901 AC: 13720 AN: 152232 Hom.: 828 Cov.: 32 AF XY: 0.0926 AC XY: 6888 AN XY: 74420

African (AFR) AF: 0.0209 AC: 870 AN: 41538

American (AMR) AF: 0.0673 AC: 1029 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 313 AN: 3472

East Asian (EAS) AF: 0.158 AC: 820 AN: 5188

South Asian (SAS) AF: 0.125 AC: 603 AN: 4830

European-Finnish (FIN) AF: 0.163 AC: 1722 AN: 10586

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7916 AN: 68002

Other (OTH) AF: 0.0903 AC: 191 AN: 2114

Alfa AF: 0.0775 Hom.: 221

Bravo AF: 0.0822

Asia WGS AF: 0.127 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5750609; hg19: chr22-38884775;