rs3093978

Variant names:

• chr6-31530720-C-A
• rs3093978
• NM_004640.7:c.1270+59G>T

Variant summary

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

The NM_004640.7(DDX39B):​c.1270+59G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,586,998 control chromosomes in the GnomAD database, including 545,605 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 0.85 (54720 hom., cov: 30)
  • Exomes 𝑓: 0.83 (490885 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413
• Publications: 36 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• 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 rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.1270+59G>T		intron_variant	Intron 10 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.1270+59G>T		intron_variant	Intron 10 of 10		NP_542165.1
DDX39B	NR_037852.2	n.1235+59G>T		intron_variant	Intron 8 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.2073+59G>T		intron_variant	Intron 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.1270+59G>T		intron_variant	Intron 10 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*1484+59G>T		intron_variant	Intron 12 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128780 AN: 151988 Hom.: 54663 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.859

GnomAD4 exome AF: 0.826 AC: 1185096 AN: 1434892 Hom.: 490885 Cov.: 32 AF XY: 0.830 AC XY: 590609 AN XY: 711518

African (AFR) AF: 0.885 AC: 29301 AN: 33122

American (AMR) AF: 0.865 AC: 38234 AN: 44192

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 23910 AN: 25434

East Asian (EAS) AF: 0.921 AC: 36248 AN: 39374

South Asian (SAS) AF: 0.926 AC: 78755 AN: 85044

European-Finnish (FIN) AF: 0.818 AC: 36671 AN: 44824

Middle Eastern (MID) AF: 0.913 AC: 4113 AN: 4506

European-Non Finnish (NFE) AF: 0.808 AC: 888299 AN: 1099080

Other (OTH) AF: 0.836 AC: 49565 AN: 59316

GnomAD4 genome AF: 0.847 AC: 128895 AN: 152106 Hom.: 54720 Cov.: 30 AF XY: 0.852 AC XY: 63332 AN XY: 74372

African (AFR) AF: 0.876 AC: 36334 AN: 41468

American (AMR) AF: 0.868 AC: 13273 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3264 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4798 AN: 5182

South Asian (SAS) AF: 0.923 AC: 4459 AN: 4830

European-Finnish (FIN) AF: 0.824 AC: 8713 AN: 10576

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55226 AN: 67978

Other (OTH) AF: 0.860 AC: 1808 AN: 2102

Alfa AF: 0.834 Hom.: 154839

Bravo AF: 0.851

Asia WGS AF: 0.866 AC: 3012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.64
DANN	Benign	0.66
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3093978; hg19: chr6-31498497;