chr6-31530261-TA-T

Variant names:

• chr6-31530261-TA-T
• rs3219189
• ENST00000376185.5:n.*1673delT

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

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]

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]

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376185.5. 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.*172delT		3_prime_UTR	Exon 11 of 11	NP_004631.1
	DDX39B	NR_037852.2		n.1424delT		non_coding_transcript_exon	Exon 9 of 9
	ATP6V1G2-DDX39B	NR_037853.1		n.2262delT		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.*1673delT		non_coding_transcript_exon	Exon 13 of 13	ENSP00000365356.1
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.*172delT		3_prime_UTR	Exon 11 of 11	ENSP00000379475.1
	DDX39B	ENST00000458640.5	TSL:1	c.*172delT		3_prime_UTR	Exon 11 of 11	ENSP00000416269.1

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

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

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

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: 6 AN: 290

European-Non Finnish (NFE) AF: 0.0279 AC: 1860 AN: 66652

Other (OTH) AF: 0.0303 AC: 61 AN: 2016

Alfa AF: 0.0131 Hom.: 7

Bravo AF: 0.0224

Asia WGS AF: 0.0650 AC: 224 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
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: rs3219189; hg19: chr6-31498038;