NM_024415.3:c.335-1186C>T

Variant names:

• chr5-55766695-C-T
• rs10035707
• NM_024415.3:c.335-1186C>T

Variant summary

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

The NM_024415.3(DDX4):​c.335-1186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,862 control chromosomes in the GnomAD database, including 13,975 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 (13975 hom., cov: 31)
• Consequence: DDX4 NM_024415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024415.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX4	NM_024415.3	MANE Select	c.335-1186C>T		intron	N/A	NP_077726.1	Q9NQI0-1
	DDX4	NM_001166533.2		c.334+2631C>T		intron	N/A	NP_001160005.1	Q9NQI0-4
	DDX4	NM_001142549.2		c.335-1186C>T		intron	N/A	NP_001136021.1	Q9NQI0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX4	ENST00000505374.6	TSL:1 MANE Select	c.335-1186C>T		intron	N/A	ENSP00000424838.1	Q9NQI0-1
	DDX4	ENST00000353507.9	TSL:1	c.335-1186C>T		intron	N/A	ENSP00000334167.7	Q9NQI0-2
	DDX4	ENST00000514278.6	TSL:5	c.334+2631C>T		intron	N/A	ENSP00000425359.2	Q9NQI0-4

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61449 AN: 151744 Hom.: 13934 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.405 AC: 61552 AN: 151862 Hom.: 13975 Cov.: 31 AF XY: 0.404 AC XY: 29945 AN XY: 74208

African (AFR) AF: 0.594 AC: 24592 AN: 41390

American (AMR) AF: 0.487 AC: 7417 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1178 AN: 3464

East Asian (EAS) AF: 0.477 AC: 2456 AN: 5150

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4822

European-Finnish (FIN) AF: 0.255 AC: 2686 AN: 10526

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

European-Non Finnish (NFE) AF: 0.302 AC: 20558 AN: 67962

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.342 Hom.: 16212

Bravo AF: 0.439

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.47
PhyloP100		0.30
PromoterAI		0.0038	Neutral
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: rs10035707; hg19: chr5-55062523;