rs7730742

Variant names:

• chr5-55764828-G-A
• rs7730742
• NM_024415.3:c.334+764G>A

Variant summary

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

The NM_024415.3(DDX4):​c.334+764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,956 control chromosomes in the GnomAD database, including 14,043 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 0.41 (14043 hom., cov: 32)
• Consequence: DDX4 NM_024415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 1 publications found

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]

SLC38A9 (HGNC:26907): (solute carrier family 38 member 9) Enables L-arginine transmembrane transporter activity and L-leucine transmembrane transporter activity. Involved in amino acid transmembrane transport; cellular response to amino acid stimulus; and positive regulation of TOR signaling. Located in late endosome and lysosomal membrane. Is integral component of lysosomal membrane. Colocalizes with Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A9 Gene-Disease associations (from GenCC):

• lysosomal storage disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX4	NM_024415.3	c.334+764G>A		intron_variant	Intron 6 of 21	ENST00000505374.6	NP_077726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX4	ENST00000505374.6	c.334+764G>A		intron_variant	Intron 6 of 21	1	NM_024415.3	ENSP00000424838.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61629 AN: 151838 Hom.: 14002 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.406 AC: 61732 AN: 151956 Hom.: 14043 Cov.: 32 AF XY: 0.404 AC XY: 30047 AN XY: 74302

African (AFR) AF: 0.594 AC: 24630 AN: 41462

American (AMR) AF: 0.489 AC: 7465 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1177 AN: 3462

East Asian (EAS) AF: 0.478 AC: 2468 AN: 5168

South Asian (SAS) AF: 0.308 AC: 1485 AN: 4824

European-Finnish (FIN) AF: 0.255 AC: 2692 AN: 10550

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20626 AN: 67898

Other (OTH) AF: 0.392 AC: 828 AN: 2112

Alfa AF: 0.338 Hom.: 13084

Bravo AF: 0.439

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		-0.077
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: rs7730742; hg19: chr5-55060656;