6-31538847-T-C

Variant names:

• chr6-31538847-T-C
• rs1129640
• NM_004640.7:c.348A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004640.7(DDX39B):​c.348A>G​(p.Val116Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,613,368 control chromosomes in the GnomAD database, including 555,011 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 (54737 hom., cov: 32)
  • Exomes 𝑓: 0.83 (500274 hom.)
• Consequence: DDX39B NM_004640.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 46 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.072 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004640.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	NM_004640.7	MANE Select	c.348A>G	p.Val116Val	synonymous	Exon 4 of 11	NP_004631.1
	DDX39B	NM_080598.6		c.348A>G	p.Val116Val	synonymous	Exon 4 of 11	NP_542165.1
	ATP6V1G2-DDX39B	NR_037853.1		n.1151A>G		non_coding_transcript_exon	Exon 6 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.348A>G	p.Val116Val	synonymous	Exon 4 of 11	ENSP00000379475.1
	DDX39B	ENST00000458640.5	TSL:1	c.348A>G	p.Val116Val	synonymous	Exon 4 of 11	ENSP00000416269.1
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.*562A>G		non_coding_transcript_exon	Exon 6 of 13	ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128815 AN: 152030 Hom.: 54680 Cov.: 32

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: 0.813

Gnomad OTH AF: 0.861

GnomAD2 exomes AF: 0.856 AC: 215141 AN: 251422 AF XY: 0.861

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.944

Gnomad EAS exome AF: 0.931

Gnomad FIN exome AF: 0.816

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.853

GnomAD4 exome AF: 0.826 AC: 1207288 AN: 1461220 Hom.: 500274 Cov.: 51 AF XY: 0.830 AC XY: 603601 AN XY: 726936

African (AFR) AF: 0.884 AC: 29568 AN: 33466

American (AMR) AF: 0.865 AC: 38672 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 24561 AN: 26134

East Asian (EAS) AF: 0.920 AC: 36540 AN: 39698

South Asian (SAS) AF: 0.926 AC: 79879 AN: 86252

European-Finnish (FIN) AF: 0.816 AC: 43595 AN: 53408

Middle Eastern (MID) AF: 0.913 AC: 5265 AN: 5768

European-Non Finnish (NFE) AF: 0.809 AC: 898749 AN: 1111410

Other (OTH) AF: 0.836 AC: 50459 AN: 60368

GnomAD4 genome AF: 0.847 AC: 128930 AN: 152148 Hom.: 54737 Cov.: 32 AF XY: 0.852 AC XY: 63341 AN XY: 74376

African (AFR) AF: 0.876 AC: 36336 AN: 41486

American (AMR) AF: 0.868 AC: 13261 AN: 15274

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

East Asian (EAS) AF: 0.926 AC: 4805 AN: 5190

South Asian (SAS) AF: 0.923 AC: 4453 AN: 4822

European-Finnish (FIN) AF: 0.824 AC: 8715 AN: 10578

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

European-Non Finnish (NFE) AF: 0.812 AC: 55258 AN: 68010

Other (OTH) AF: 0.862 AC: 1818 AN: 2110

Alfa AF: 0.831 Hom.: 175580

Bravo AF: 0.851

Asia WGS AF: 0.866 AC: 3013 AN: 3478

EpiCase AF: 0.835

EpiControl AF: 0.849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		-0.072
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs1129640; hg19: chr6-31506624; COSMIC: COSV63331070; COSMIC: COSV63331070;