NM_007204.5:c.1907T>C

Variant names:

• chr1-111766331-T-C
• rs197412
• NM_007204.5:c.1907T>C

Variant summary

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

The NM_007204.5(DDX20):​c.1907T>C​(p.Ile636Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,613,432 control chromosomes in the GnomAD database, including 139,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.48 (18790 hom., cov: 32)
  • Exomes 𝑓: 0.40 (121035 hom.)
• Consequence: DDX20 NM_007204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 83 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 (MetaRNN=2.599391E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX20	NM_007204.5	MANE Select	c.1907T>C	p.Ile636Thr	missense	Exon 11 of 11	NP_009135.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX20	ENST00000369702.5	TSL:1 MANE Select	c.1907T>C	p.Ile636Thr	missense	Exon 11 of 11	ENSP00000358716.4	Q9UHI6-1
	DDX20	ENST00000937510.1		c.2003T>C	p.Ile668Thr	missense	Exon 12 of 12	ENSP00000607569.1
	DDX20	ENST00000679724.1		c.1907T>C	p.Ile636Thr	missense	Exon 12 of 12	ENSP00000505857.1	Q9UHI6-1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72961 AN: 151948 Hom.: 18749 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.475

GnomAD2 exomes AF: 0.426 AC: 106929 AN: 250918 AF XY: 0.413

Gnomad AFR exome AF: 0.688

Gnomad AMR exome AF: 0.530

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.345

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.402 AC: 587222 AN: 1461366 Hom.: 121035 Cov.: 46 AF XY: 0.399 AC XY: 289877 AN XY: 726986

African (AFR) AF: 0.698 AC: 23381 AN: 33474

American (AMR) AF: 0.523 AC: 23386 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 9301 AN: 26126

East Asian (EAS) AF: 0.356 AC: 14150 AN: 39698

South Asian (SAS) AF: 0.337 AC: 29106 AN: 86242

European-Finnish (FIN) AF: 0.463 AC: 24650 AN: 53274

Middle Eastern (MID) AF: 0.390 AC: 2250 AN: 5768

European-Non Finnish (NFE) AF: 0.393 AC: 436650 AN: 1111692

Other (OTH) AF: 0.403 AC: 24348 AN: 60384

GnomAD4 genome AF: 0.481 AC: 73068 AN: 152066 Hom.: 18790 Cov.: 32 AF XY: 0.477 AC XY: 35466 AN XY: 74324

African (AFR) AF: 0.682 AC: 28268 AN: 41478

American (AMR) AF: 0.462 AC: 7060 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1215 AN: 3466

East Asian (EAS) AF: 0.349 AC: 1805 AN: 5176

South Asian (SAS) AF: 0.326 AC: 1570 AN: 4822

European-Finnish (FIN) AF: 0.448 AC: 4729 AN: 10558

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27059 AN: 67966

Other (OTH) AF: 0.473 AC: 1000 AN: 2114

Alfa AF: 0.427 Hom.: 40239

Bravo AF: 0.492

TwinsUK AF: 0.393 AC: 1456

ALSPAC AF: 0.388 AC: 1497

ESP6500AA AF: 0.670 AC: 2950

ESP6500EA AF: 0.389 AC: 3345

ExAC AF: 0.427 AC: 51820

Asia WGS AF: 0.349 AC: 1219 AN: 3478

EpiCase AF: 0.394

EpiControl AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.68
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.092	T
MetaRNN	Benign	0.0000026	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.8	N
PhyloP100		1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.12
Sift	Benign	0.65	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.10
ClinPred		0.0037	T
GERP RS		3.9
Varity_R		0.013
gMVP		0.074
Mutation Taster		=96/4	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: rs197412; hg19: chr1-112308953; COSMIC: COSV63780126; COSMIC: COSV63780126;