12-113169697-T-C

Variant names:

• chr12-113169697-T-C
• rs2384207
• NM_024072.4:c.1414+73A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024072.4(DDX54):​c.1414+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 1,546,162 control chromosomes in the GnomAD database, including 26,679 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 0.21 (3564 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23115 hom.)
• Consequence: DDX54 NM_024072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 13 publications found

Genes affected

DDX54 (HGNC:20084): (DEAD-box helicase 54) 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 nucleolar protein encoded by this gene interacts in a hormone-dependent manner with nuclear receptors, and represses their transcriptional activity. Alternative splice variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024072.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX54	NM_024072.4	MANE Select	c.1414+73A>G		intron	N/A	NP_076977.3
	DDX54	NM_001111322.2		c.1414+73A>G		intron	N/A	NP_001104792.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX54	ENST00000306014.10	TSL:1 MANE Select	c.1414+73A>G		intron	N/A	ENSP00000304072.5
	DDX54	ENST00000314045.11	TSL:1	c.1414+73A>G		intron	N/A	ENSP00000323858.7

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31905 AN: 152002 Hom.: 3540 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.178 AC: 248790 AN: 1394042 Hom.: 23115 AF XY: 0.178 AC XY: 122897 AN XY: 689018

African (AFR) AF: 0.284 AC: 8869 AN: 31188

American (AMR) AF: 0.132 AC: 4694 AN: 35526

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4777 AN: 23022

East Asian (EAS) AF: 0.258 AC: 9993 AN: 38676

South Asian (SAS) AF: 0.170 AC: 13333 AN: 78562

European-Finnish (FIN) AF: 0.221 AC: 11382 AN: 51482

Middle Eastern (MID) AF: 0.174 AC: 844 AN: 4854

European-Non Finnish (NFE) AF: 0.171 AC: 183967 AN: 1073462

Other (OTH) AF: 0.191 AC: 10931 AN: 57270

GnomAD4 genome AF: 0.210 AC: 31970 AN: 152120 Hom.: 3564 Cov.: 32 AF XY: 0.212 AC XY: 15754 AN XY: 74344

African (AFR) AF: 0.294 AC: 12213 AN: 41492

American (AMR) AF: 0.161 AC: 2458 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1213 AN: 5176

South Asian (SAS) AF: 0.171 AC: 824 AN: 4816

European-Finnish (FIN) AF: 0.228 AC: 2415 AN: 10570

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11483 AN: 67996

Other (OTH) AF: 0.196 AC: 414 AN: 2114

Alfa AF: 0.184 Hom.: 4001

Bravo AF: 0.209

Asia WGS AF: 0.229 AC: 796 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.79
PhyloP100		-1.9
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: rs2384207; hg19: chr12-113607502;