Genetic Variant NM_004640.7:c.1271-18dupG (chr6-31530467-G-GC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004640.7(DDX39B):c.1271-18dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,612,418 control chromosomes in the GnomAD database, including 11,986 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.099 ( 857 hom., cov: 29)

Exomes 𝑓: 0.11 ( 11129 hom. )

Consequence

DDX39B
NM_004640.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.396

Variant links:

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]

DDX39B links:

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]

ATP6V1G2-DDX39B links:

MCCD1 (HGNC:20668): (mitochondrial coiled-coil domain 1) Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MCCD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7 link	c.1271-18dupG		intron_variant	Intron 10 of 10	ENST00000396172.6	NP_004631.1	Q13838-1A0A024RCM3
MCCD1	NM_001011700.3 link	c.532_533insC		downstream_gene_variant		ENST00000376191.3	NP_001011700.2	P59942A0A1U9X802

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DDX39B	ENST00000396172.6 link	c.1271-18dupG	intron_variant	Intron 10 of 10	1	NM_004640.7	ENSP00000379475.1	Q13838-1
ATP6V1G2-DDX39B	ENST00000376185.5 link	n.*1485-18dupG	intron_variant	Intron 12 of 12	2		ENSP00000365356.1	F2Z307
MCCD1	ENST00000376191.3 link	c.532_533insC	downstream_gene_variant		1	NM_001011700.3	ENSP00000365362.2	P59942

Frequencies

GnomAD3 genomes

AF:

0.0994

AC:

15107

AN:

151992

Hom.:

855

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.0629

Gnomad SAS

AF:

0.0377

Gnomad FIN

AF:

0.0811

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.0724

GnomAD3 exomes

AF:

0.0813

AC:

20014

AN:

246126

Hom.:

1077

AF XY:

0.0800

AC XY:

10729

AN XY:

134168

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0298

Gnomad ASJ exome

AF:

0.0401

Gnomad EAS exome

AF:

0.0887

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.0792

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0723

GnomAD4 exome

AF:

0.114

AC:

166961

AN:

1460308

Hom.:

11129

Cov.:

AF XY:

0.112

AC XY:

81109

AN XY:

726490

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.0318

Gnomad4 ASJ exome

AF:

0.0436

Gnomad4 EAS exome

AF:

0.0404

Gnomad4 SAS exome

AF:

0.0416

Gnomad4 FIN exome

AF:

0.0834

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0994

AC:

15113

AN:

152110

Hom.:

857

Cov.:

AF XY:

0.0947

AC XY:

7042

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.0436

Gnomad4 ASJ

AF:

0.0429

Gnomad4 EAS

AF:

0.0630

Gnomad4 SAS

AF:

0.0379

Gnomad4 FIN

AF:

0.0811

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.0716

Alfa

AF:

0.101

Hom.:

212

Bravo

AF:

0.0979

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over