chr17-64500552-A-C

Variant names:

• chr17-64500552-A-C
• rs1140409
• NM_004396.5:c.1438T>G

Variant summary

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

The NM_004396.5(DDX5):​c.1438T>G​(p.Ser480Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 1,612,270 control chromosomes in the GnomAD database, including 3,143 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.050 (264 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2879 hom.)
• Consequence: DDX5 NM_004396.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• Publications: 25 publications found

Genes affected

DDX5 (HGNC:2746): (DEAD-box helicase 5) This gene encodes a member of the DEAD box family of RNA helicases that are involved in a variety of cellular processes as a result of its role as an adaptor molecule, promoting interactions with a large number of other factors. This protein is involved in pathways that include the alteration of RNA structures, plays a role as a coregulator of transcription, a regulator of splicing, and in the processing of small noncoding RNAs. Members of this family contain nine conserved motifs, including the conserved Asp-Glu-Ala-Asp (DEAD) motif, important to ATP binding and hydrolysis as well as RNA binding and unwinding activities. Dysregulation of this gene may play a role in cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2017]

MIR3064 (HGNC:41652): (microRNA 3064) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014832616).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004396.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX5	NM_004396.5	MANE Select	c.1438T>G	p.Ser480Ala	missense	Exon 12 of 13	NP_004387.1
	DDX5	NM_001320595.2		c.1438T>G	p.Ser480Ala	missense	Exon 13 of 14	NP_001307524.1
	DDX5	NM_001320596.3		c.1438T>G	p.Ser480Ala	missense	Exon 13 of 14	NP_001307525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX5	ENST00000225792.10	TSL:1 MANE Select	c.1438T>G	p.Ser480Ala	missense	Exon 12 of 13	ENSP00000225792.5
	DDX5	ENST00000578804.5	TSL:1	c.1438T>G	p.Ser480Ala	missense	Exon 12 of 13	ENSP00000462885.1
	DDX5	ENST00000450599.7	TSL:2	c.1438T>G	p.Ser480Ala	missense	Exon 13 of 14	ENSP00000403085.3

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7587 AN: 152220 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0942

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.0545

GnomAD2 exomes AF: 0.0540 AC: 13463 AN: 249176 AF XY: 0.0558

Gnomad AFR exome AF: 0.00961

Gnomad AMR exome AF: 0.0260

Gnomad ASJ exome AF: 0.0874

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0866

Gnomad NFE exome AF: 0.0732

Gnomad OTH exome AF: 0.0671

GnomAD4 exome AF: 0.0599 AC: 87467 AN: 1459932 Hom.: 2879 Cov.: 31 AF XY: 0.0601 AC XY: 43645 AN XY: 726208

African (AFR) AF: 0.00926 AC: 310 AN: 33460

American (AMR) AF: 0.0271 AC: 1211 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2263 AN: 26056

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39688

South Asian (SAS) AF: 0.0355 AC: 3050 AN: 86012

European-Finnish (FIN) AF: 0.0882 AC: 4704 AN: 53348

Middle Eastern (MID) AF: 0.0731 AC: 421 AN: 5762

European-Non Finnish (NFE) AF: 0.0648 AC: 72003 AN: 1110650

Other (OTH) AF: 0.0580 AC: 3500 AN: 60330

GnomAD4 genome AF: 0.0498 AC: 7584 AN: 152338 Hom.: 264 Cov.: 32 AF XY: 0.0505 AC XY: 3760 AN XY: 74482

African (AFR) AF: 0.0102 AC: 425 AN: 41584

American (AMR) AF: 0.0409 AC: 626 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4830

European-Finnish (FIN) AF: 0.0942 AC: 1000 AN: 10620

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0709 AC: 4822 AN: 68018

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

Alfa AF: 0.0622 Hom.: 1047

Bravo AF: 0.0429

TwinsUK AF: 0.0564 AC: 209

ALSPAC AF: 0.0589 AC: 227

ESP6500AA AF: 0.0116 AC: 51

ESP6500EA AF: 0.0715 AC: 615

ExAC AF: 0.0561 AC: 6815

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.5
PrimateAI	Uncertain	0.54	T
REVEL	Benign	0.17
Sift4G	Benign	0.21	T
Polyphen		0.024	B
Vest4		0.080
ClinPred		0.014	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.096
gMVP		0.29
Mutation Taster		=98/2	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: rs1140409; hg19: chr17-62496670; COSMIC: COSV107310788; COSMIC: COSV107310788;