5-55786646-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_024415.3(DDX4):c.993C>T(p.Cys331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,610,654 control chromosomes in the GnomAD database, including 97,204 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 0.40 (13953 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83251 hom.)
• Consequence: DDX4 NM_024415.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

Genes affected

DDX4 (HGNC:18700): (DEAD-box helicase 4) 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. This gene encodes a DEAD box protein, which is a homolog of VASA proteins in Drosophila and several other species. The gene is specifically expressed in the germ cell lineage in both sexes and functions in germ cell development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX4	NM_024415.3	c.993C>T	p.Cys331=	synonymous_variant	14/22	ENST00000505374.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX4	ENST00000505374.6	c.993C>T	p.Cys331=	synonymous_variant	14/22	1	NM_024415.3	P1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61428 AN: 151808 Hom.: 13913 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.308

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.393

GnomAD3 exomes AF: 0.378 AC: 94927 AN: 251222 Hom.: 20289 AF XY: 0.361 AC XY: 48968 AN XY: 135774

Gnomad AFR exome AF: 0.600

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.325

Gnomad EAS exome AF: 0.482

Gnomad SAS exome AF: 0.306

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.328 AC: 478387 AN: 1458728 Hom.: 83251 Cov.: 32 AF XY: 0.325 AC XY: 236059 AN XY: 725854

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.405 AC: 61528 AN: 151926 Hom.: 13953 Cov.: 32 AF XY: 0.403 AC XY: 29975 AN XY: 74290

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.390

Alfa AF: 0.333 Hom.: 14625

Bravo AF: 0.438

Asia WGS AF: 0.410 AC: 1427 AN: 3478

EpiCase AF: 0.306

EpiControl AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	13
Dann	Benign	0.68

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: rs957459; hg19: chr5-55082474; COSMIC: COSV61754181; COSMIC: COSV61754181;