rs3093948

Positions:

• chr6-31533636-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004640.7(DDX39B):​c.736-725T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,404 control chromosomes in the GnomAD database, including 54,415 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 0.84 (54320 hom., cov: 31)
  • Exomes 𝑓: 0.85 (95 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

DDX39B (HGNC:13917): (DExD-box helicase 39B) This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

DDX39B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.736-725T>C		intron_variant		ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.736-725T>C		intron_variant			NP_542165.1
DDX39B	NR_037852.2	n.701-725T>C		intron_variant
ATP6V1G2-DDX39B	NR_037853.1	n.1539-725T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.736-725T>C		intron_variant		1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*950-725T>C		intron_variant		2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128312 AN: 152032 Hom.: 54263 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.856

GnomAD4 exome AF: 0.854 AC: 217 AN: 254 Hom.: 95 Cov.: 0 AF XY: 0.902 AC XY: 110 AN XY: 122

Gnomad4 AMR exome AF: 0.688

Gnomad4 SAS exome AF: 0.938

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.835

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.844 AC: 128427 AN: 152150 Hom.: 54320 Cov.: 31 AF XY: 0.848 AC XY: 63033 AN XY: 74364

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.808

Gnomad4 OTH AF: 0.857

Alfa AF: 0.825 Hom.: 39698

Bravo AF: 0.848

Asia WGS AF: 0.865 AC: 3007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.50

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: rs3093948; hg19: chr6-31501413;