chr12-48829936-C-T

Position:

• chr12-48829936-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004818.3(DDX23):​c.*533G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 330,294 control chromosomes in the GnomAD database, including 27,493 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11385 hom., cov: 32)
  • Exomes 𝑓: 0.42 (16108 hom.)
• Consequence: DDX23 NM_004818.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX23	NM_004818.3	c.*533G>A		3_prime_UTR_variant	17/17	ENST00000308025.8	NP_004809.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX23	ENST00000308025.8	c.*533G>A		3_prime_UTR_variant	17/17	1	NM_004818.3	ENSP00000310723	P1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55674 AN: 151958 Hom.: 11380 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.416 AC: 74104 AN: 178216 Hom.: 16108 Cov.: 0 AF XY: 0.410 AC XY: 39808 AN XY: 97154

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.495

Gnomad4 EAS exome AF: 0.570

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.366 AC: 55690 AN: 152078 Hom.: 11385 Cov.: 32 AF XY: 0.369 AC XY: 27426 AN XY: 74350

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.390

Alfa AF: 0.436 Hom.: 15017

Bravo AF: 0.355

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.076
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs7164; hg19: chr12-49223719;