rs7164

Variant names:

• chr12-48829936-C-T
• rs7164
• NM_004818.3:c.*533G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

DDX23 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDX23	NM_004818.3	c.*533G>A		3_prime_UTR_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.*533G>A		3_prime_UTR_variant	Exon 17 of 17	1	NM_004818.3	ENSP00000310723.2

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

African (AFR) AF: 0.171 AC: 855 AN: 4992

American (AMR) AF: 0.346 AC: 2745 AN: 7934

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 2021 AN: 4080

East Asian (EAS) AF: 0.570 AC: 4211 AN: 7394

South Asian (SAS) AF: 0.357 AC: 12805 AN: 35830

European-Finnish (FIN) AF: 0.441 AC: 3618 AN: 8204

Middle Eastern (MID) AF: 0.398 AC: 245 AN: 616

European-Non Finnish (NFE) AF: 0.438 AC: 44002 AN: 100576

Other (OTH) AF: 0.419 AC: 3602 AN: 8590

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

African (AFR) AF: 0.175 AC: 7246 AN: 41478

American (AMR) AF: 0.377 AC: 5762 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1773 AN: 3470

East Asian (EAS) AF: 0.581 AC: 2998 AN: 5158

South Asian (SAS) AF: 0.369 AC: 1777 AN: 4814

European-Finnish (FIN) AF: 0.433 AC: 4582 AN: 10588

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30208 AN: 67972

Other (OTH) AF: 0.390 AC: 824 AN: 2112

Alfa AF: 0.424 Hom.: 18587

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
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7164; hg19: chr12-49223719;