12-48831190-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004818.3(DDX23):​c.2191C>G​(p.Gln731Glu) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

DDX23
NM_004818.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.08
Variant links:
Genes affected
DDX23 (HGNC:17347): (DEAD-box helicase 23) This gene encodes a member of the DEAD box protein family. 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. The protein encoded by this gene is a component of the U5 snRNP complex; it may facilitate conformational changes in the spliceosome during nuclear pre-mRNA splicing. An alternatively spliced transcript variant has been found for this gene, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27824602).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDX23NM_004818.3 linkuse as main transcriptc.2191C>G p.Gln731Glu missense_variant 16/17 ENST00000308025.8 NP_004809.2 Q9BUQ8-1A0A024R0Z3B3KY11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDX23ENST00000308025.8 linkuse as main transcriptc.2191C>G p.Gln731Glu missense_variant 16/171 NM_004818.3 ENSP00000310723.2 Q9BUQ8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

DDX23-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 18, 2024The DDX23 c.2191C>G variant is predicted to result in the amino acid substitution p.Gln731Glu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.38
N
REVEL
Benign
0.20
Sift
Benign
0.16
T
Sift4G
Benign
0.13
T
Polyphen
0.34
B
Vest4
0.34
MutPred
0.56
Loss of stability (P = 0.1535);
MVP
0.39
MPC
1.6
ClinPred
0.72
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.94

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-49224973; API