rs3215391

Variant names:

• chr6-31530602-CA-C
• rs3215391
• NM_004640.7:c.1271-153delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004640.7(DDX39B):​c.1271-153delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (50931 hom., cov: 0)
  • Exomes 𝑓: 0.79 (356821 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 3 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.1271-153delT		intron_variant	Intron 10 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.1271-153delT		intron_variant	Intron 10 of 10		NP_542165.1
DDX39B	NR_037852.2	n.1236-153delT		intron_variant	Intron 8 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.2074-153delT		intron_variant	Intron 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.1271-153delT		intron_variant	Intron 10 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*1485-153delT		intron_variant	Intron 12 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 123955 AN: 151194 Hom.: 50878 Cov.: 0

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.833

GnomAD4 exome AF: 0.790 AC: 899477 AN: 1137880 Hom.: 356821 Cov.: 0 AF XY: 0.792 AC XY: 448561 AN XY: 566268

African (AFR) AF: 0.875 AC: 22601 AN: 25818

American (AMR) AF: 0.842 AC: 26936 AN: 31988

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 17237 AN: 19810

East Asian (EAS) AF: 0.798 AC: 29211 AN: 36626

South Asian (SAS) AF: 0.843 AC: 57467 AN: 68140

European-Finnish (FIN) AF: 0.757 AC: 35719 AN: 47182

Middle Eastern (MID) AF: 0.841 AC: 3341 AN: 3972

European-Non Finnish (NFE) AF: 0.781 AC: 667775 AN: 855348

Other (OTH) AF: 0.800 AC: 39190 AN: 48996

GnomAD4 genome AF: 0.820 AC: 124069 AN: 151314 Hom.: 50931 Cov.: 0 AF XY: 0.822 AC XY: 60750 AN XY: 73898

African (AFR) AF: 0.868 AC: 35835 AN: 41296

American (AMR) AF: 0.848 AC: 12914 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3025 AN: 3432

East Asian (EAS) AF: 0.853 AC: 4356 AN: 5108

South Asian (SAS) AF: 0.854 AC: 4071 AN: 4766

European-Finnish (FIN) AF: 0.760 AC: 7930 AN: 10430

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53193 AN: 67744

Other (OTH) AF: 0.833 AC: 1755 AN: 2106

Alfa AF: 0.794 Hom.: 5179

Bravo AF: 0.828

Asia WGS AF: 0.805 AC: 2785 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27
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: rs3215391; hg19: chr6-31498379;