Genetic Variant ATP6V1G2-DDX39B:n.*1673delT (chr6-31530261-TA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The ENST00000376185.5(ATP6V1G2-DDX39B):n.*1673delT variant causes a non coding transcript exon 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

ATP6V1G2-DDX39B
ENST00000376185.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

Publications

0 publications found

Variant links:

Genes affected

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:

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:

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

MCCD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDX39B	NM_004640.7 link	c.*172delT		3_prime_UTR_variant	Exon 11 of 11	ENST00000396172.6	NP_004631.1
MCCD1	NM_001011700.3 link	c.*327delA		downstream_gene_variant		ENST00000376191.3	NP_001011700.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ATP6V1G2-DDX39B	ENST00000376185.5 link	n.*1673delT	non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000365356.1
DDX39B	ENST00000396172.6 link	c.*172delT	3_prime_UTR_variant	Exon 11 of 11	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5 link	n.*1673delT	3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000365356.1
MCCD1	ENST00000376191.3 link	c.*327delA	downstream_gene_variant		1	NM_001011700.3	ENSP00000365362.2

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4285

AN:

146438

Hom.:

104

Cov.:

show subpopulations

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.:

AF XY:

0.0384

AC XY:

14210

AN XY:

369896

show subpopulations

African (AFR)

AF:

0.00818

AC:

140

AN:

17122

American (AMR)

AF:

0.0251

AC:

454

AN:

18096

Ashkenazi Jewish (ASJ)

AF:

0.0696

AC:

1055

AN:

15148

East Asian (EAS)

AF:

0.130

AC:

4121

AN:

31666

South Asian (SAS)

AF:

0.0810

AC:

4042

AN:

49916

European-Finnish (FIN)

AF:

0.0580

AC:

2479

AN:

42756

Middle Eastern (MID)

AF:

0.0679

AC:

168

AN:

2476

European-Non Finnish (NFE)

AF:

0.0251

AC:

13098

AN:

521562

Other (OTH)

AF:

0.0339

AC:

1178

AN:

34704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1287

2575

3862

5150

6437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

358

716

1074

1432

1790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0293

AC:

4287

AN:

146528

Hom.:

104

Cov.:

AF XY:

0.0319

AC XY:

2273

AN XY:

71242

show subpopulations

African (AFR)

AF:

0.00855

AC:

338

AN:

39554

American (AMR)

AF:

0.0220

AC:

320

AN:

14572

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

229

AN:

3412

East Asian (EAS)

AF:

0.0780

AC:

391

AN:

5014

South Asian (SAS)

AF:

0.0787

AC:

367

AN:

4664

European-Finnish (FIN)

AF:

0.0735

AC:

696

AN:

9472

Middle Eastern (MID)

AF:

0.0207

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0279

AC:

1860

AN:

66652

Other (OTH)

AF:

0.0303

AC:

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

177

354

532

709

886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0224

Asia WGS

AF:

0.0650

AC:

224

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-31530261-TAAAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over