rs138457

Variant names:

• chr22-38502046-T-C
• rs138457
• NM_006386.5:c.288-766A>G

Variant summary

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

The NM_006386.5(DDX17):​c.288-766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,144 control chromosomes in the GnomAD database, including 26,005 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 0.58 (26005 hom., cov: 33)
• Consequence: DDX17 NM_006386.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX17	NM_006386.5	c.288-766A>G		intron_variant	Intron 1 of 12	ENST00000403230.3	NP_006377.2
DDX17	NM_001098504.2	c.288-766A>G		intron_variant	Intron 1 of 12		NP_001091974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX17	ENST00000403230.3	c.288-766A>G		intron_variant	Intron 1 of 12	1	NM_006386.5	ENSP00000385536.2

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88091 AN: 152026 Hom.: 25996 Cov.: 33

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.591

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.579 AC: 88115 AN: 152144 Hom.: 26005 Cov.: 33 AF XY: 0.579 AC XY: 43079 AN XY: 74376

African (AFR) AF: 0.461 AC: 19140 AN: 41494

American (AMR) AF: 0.669 AC: 10236 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2049 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2650 AN: 5178

South Asian (SAS) AF: 0.606 AC: 2927 AN: 4830

European-Finnish (FIN) AF: 0.632 AC: 6679 AN: 10576

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42594 AN: 67986

Other (OTH) AF: 0.586 AC: 1241 AN: 2116

Alfa AF: 0.614 Hom.: 54142

Bravo AF: 0.580

Asia WGS AF: 0.558 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.53
DANN	Benign	0.75
PhyloP100		-1.4
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: rs138457; hg19: chr22-38898051;