12-48830553-G-A

Variant names:

• chr12-48830553-G-A
• rs146973565
• NM_004818.3:c.2379C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004818.3(DDX23):​c.2379C>T​(p.Pro793Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,613,804 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (13 hom.)
• Consequence: DDX23 NM_004818.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 12-48830553-G-A is Benign according to our data. Variant chr12-48830553-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3904795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.86 with no splicing effect.
• BS2: High AC in GnomAd4 at 501 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX23	NM_004818.3	c.2379C>T	p.Pro793Pro	synonymous_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.2379C>T	p.Pro793Pro	synonymous_variant	Exon 17 of 17	1	NM_004818.3	ENSP00000310723.2

Frequencies

GnomAD3 genomes AF: 0.00330 AC: 502 AN: 152080 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00446

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00368 AC: 924 AN: 251398 AF XY: 0.00391

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00527

Gnomad NFE exome AF: 0.00483

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00396 AC: 5794 AN: 1461606 Hom.: 13 Cov.: 31 AF XY: 0.00402 AC XY: 2921 AN XY: 727114

African (AFR) AF: 0.00105 AC: 35 AN: 33470

American (AMR) AF: 0.00371 AC: 166 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00363 AC: 95 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00168 AC: 145 AN: 86238

European-Finnish (FIN) AF: 0.00616 AC: 329 AN: 53416

Middle Eastern (MID) AF: 0.00903 AC: 50 AN: 5536

European-Non Finnish (NFE) AF: 0.00426 AC: 4741 AN: 1112010

Other (OTH) AF: 0.00386 AC: 233 AN: 60376

GnomAD4 genome AF: 0.00329 AC: 501 AN: 152198 Hom.: 1 Cov.: 32 AF XY: 0.00335 AC XY: 249 AN XY: 74420

African (AFR) AF: 0.00101 AC: 42 AN: 41522

American (AMR) AF: 0.00438 AC: 67 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4812

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00446 AC: 303 AN: 68002

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00339 Hom.: 1

Bravo AF: 0.00344

EpiCase AF: 0.00529

EpiControl AF: 0.00717

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DDX23: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.2
DANN	Benign	0.83
PhyloP100		-1.9
Mutation Taster		=97/3	polymorphism

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

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Other links and lift over

dbSNP: rs146973565; hg19: chr12-49224336;