chr6-31530261-TA-T

Position:

• chr6-31530261-TA-T

Variant summary

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

The NM_004640.7(DDX39B):​c.*172delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 879,974 control chromosomes in the GnomAD database, including 958 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.029 (104 hom., cov: 31)
  • Exomes 𝑓: 0.036 (854 hom.)
• Consequence: DDX39B NM_004640.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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:):

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.*172delT		3_prime_UTR_variant	11/11	ENST00000396172.6	NP_004631.1
MCCD1	NM_001011700.3	c.*327delA		downstream_gene_variant		ENST00000376191.3	NP_001011700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172	c.*172delT		3_prime_UTR_variant	11/11	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*1673delT		non_coding_transcript_exon_variant	13/13	2		ENSP00000365356.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*1673delT		3_prime_UTR_variant	13/13	2		ENSP00000365356.1
MCCD1	ENST00000376191.3	c.*327delA		downstream_gene_variant		1	NM_001011700.3	ENSP00000365362.2

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4285 AN: 146438 Hom.: 104 Cov.: 31

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.0215

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0782

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0365 AC: 26735 AN: 733446 Hom.: 854 Cov.: 9 AF XY: 0.0384 AC XY: 14210 AN XY: 369896

Gnomad4 AFR exome AF: 0.00818

Gnomad4 AMR exome AF: 0.0251

Gnomad4 ASJ exome AF: 0.0696

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.0810

Gnomad4 FIN exome AF: 0.0580

Gnomad4 NFE exome AF: 0.0251

Gnomad4 OTH exome AF: 0.0339

GnomAD4 genome AF: 0.0293 AC: 4287 AN: 146528 Hom.: 104 Cov.: 31 AF XY: 0.0319 AC XY: 2273 AN XY: 71242

Gnomad4 AFR AF: 0.00855

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.0787

Gnomad4 FIN AF: 0.0735

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0303

Bravo AF: 0.0224

Asia WGS AF: 0.0650 AC: 224 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3219189; hg19: chr6-31498038;