rs3754025

Variant names:

• chr1-111760615-T-A
• rs3754025
• NM_007204.5:c.680+27T>A

Variant summary

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

The NM_007204.5(DDX20):​c.680+27T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,601,442 control chromosomes in the GnomAD database, including 1,423 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 0.036 (135 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1288 hom.)
• Consequence: DDX20 NM_007204.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257
• Publications: 6 publications found

Genes affected

DDX20 (HGNC:2743): (DEAD-box helicase 20) 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 spliceosome 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 has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007204.5. 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
	DDX20	NM_007204.5	MANE Select	c.680+27T>A		intron	N/A	NP_009135.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX20	ENST00000369702.5	TSL:1 MANE Select	c.680+27T>A		intron	N/A	ENSP00000358716.4
	DDX20	ENST00000679724.1		c.680+27T>A		intron	N/A	ENSP00000505857.1
	DDX20	ENST00000680627.1		c.680+27T>A		intron	N/A	ENSP00000505758.1

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5414 AN: 152212 Hom.: 133 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0397

GnomAD2 exomes AF: 0.0469 AC: 11323 AN: 241348 AF XY: 0.0442

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.0449

Gnomad EAS exome AF: 0.0738

Gnomad FIN exome AF: 0.0335

Gnomad NFE exome AF: 0.0377

Gnomad OTH exome AF: 0.0537

GnomAD4 exome AF: 0.0389 AC: 56358 AN: 1449112 Hom.: 1288 Cov.: 30 AF XY: 0.0384 AC XY: 27657 AN XY: 721096

African (AFR) AF: 0.0190 AC: 619 AN: 32602

American (AMR) AF: 0.0979 AC: 4108 AN: 41982

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 1222 AN: 25724

East Asian (EAS) AF: 0.0780 AC: 3090 AN: 39604

South Asian (SAS) AF: 0.0277 AC: 2330 AN: 84082

European-Finnish (FIN) AF: 0.0347 AC: 1848 AN: 53298

Middle Eastern (MID) AF: 0.0613 AC: 350 AN: 5712

European-Non Finnish (NFE) AF: 0.0365 AC: 40325 AN: 1106248

Other (OTH) AF: 0.0412 AC: 2466 AN: 59860

GnomAD4 genome AF: 0.0357 AC: 5431 AN: 152330 Hom.: 135 Cov.: 32 AF XY: 0.0351 AC XY: 2612 AN XY: 74492

African (AFR) AF: 0.0215 AC: 893 AN: 41578

American (AMR) AF: 0.0596 AC: 912 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3472

East Asian (EAS) AF: 0.0726 AC: 377 AN: 5192

South Asian (SAS) AF: 0.0304 AC: 147 AN: 4828

European-Finnish (FIN) AF: 0.0300 AC: 319 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0372 AC: 2528 AN: 68024

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0378 Hom.: 24

Bravo AF: 0.0392

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.1
DANN	Benign	0.71
PhyloP100		0.26
Mutation Taster		=100/0	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: rs3754025; hg19: chr1-112303237; COSMIC: COSV107473397; COSMIC: COSV107473397;