12-113169697-T-C

Position:

• chr12-113169697-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX54	NM_024072.4	c.1414+73A>G		intron_variant		ENST00000306014.10
DDX54	NM_001111322.2	c.1414+73A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX54	ENST00000306014.10	c.1414+73A>G		intron_variant		1	NM_024072.4	A1
DDX54	ENST00000314045.11	c.1414+73A>G		intron_variant		1		P3

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

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.191

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

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.196

Alfa AF: 0.178 Hom.: 382

Bravo AF: 0.209

Asia WGS AF: 0.229 AC: 796 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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