rs773622704

Variant names:

• chr1-111762756-A-C
• rs773622704
• NM_007204.5:c.1184A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-111762756-A-C
• chr1-111762756-A-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_007204.5(DDX20):​c.1184A>C​(p.His395Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H395R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX20 NM_007204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

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.1184A>C	p.His395Pro	missense	Exon 9 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.1184A>C	p.His395Pro	missense	Exon 9 of 11	ENSP00000358716.4	Q9UHI6-1
	DDX20	ENST00000937510.1		c.1280A>C	p.His427Pro	missense	Exon 10 of 12	ENSP00000607569.1
	DDX20	ENST00000679724.1		c.1184A>C	p.His395Pro	missense	Exon 10 of 12	ENSP00000505857.1	Q9UHI6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Pathogenic	4.7	H
PhyloP100		8.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-9.0	D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.89		Loss of MoRF binding (P = 0.0709)
MVP		0.97
MPC		0.56
ClinPred		1.0	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.99
Mutation Taster		=11/89	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773622704; hg19: chr1-112305378;