12-48830495-G-A

Variant names:

• chr12-48830495-G-A
• NM_004818.3:c.2437C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The NM_004818.3(DDX23):​c.2437C>T​(p.Arg813Cys) variant causes a missense change involving the alteration of a non-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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX23 NM_004818.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.29

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-48830495-G-A is Pathogenic according to our data. Variant chr12-48830495-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2664152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.31049407). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX23	NM_004818.3	c.2437C>T	p.Arg813Cys	missense_variant	Exon 17 of 17	ENST00000308025.8	NP_004809.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX23	ENST00000308025.8	c.2437C>T	p.Arg813Cys	missense_variant	Exon 17 of 17	1	NM_004818.3	ENSP00000310723.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital bilateral perisylvian syndrome Pathogenic:1

Dec 01, 2023

Center for Statistical Genetics, Columbia University

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0066	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.32	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.72	T
PROVEAN	Benign	0.93	N
REVEL	Benign	0.16
Sift	Benign	0.11	T
Sift4G	Benign	0.26	T
MutPred		0.19		Gain of catalytic residue at D148 (P = 0.0026);
MVP		0.50
ClinPred		1.0	D
GERP RS		6.0

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: chr12-49224278;