rs9267487

Variant names:

• chr6-31543573-T-C
• rs9267487
• ENST00000376185.5:n.184-1425A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000376185.5(ATP6V1G2-DDX39B):​n.184-1425A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 152,212 control chromosomes in the GnomAD database, including 272 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 0.056 (272 hom., cov: 32)
• Consequence: ATP6V1G2-DDX39B ENST00000376185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 25 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0603 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1G2-DDX39B	NR_037853.1		n.473-1425A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.184-1425A>G		intron	N/A	ENSP00000365356.1	F2Z307
	ATP6V1G2-DDX39B	ENST00000475917.1	TSL:4	n.278+1125A>G		intron	N/A
	ATP6V1G2-DDX39B	ENST00000480131.1	TSL:4	n.184-1425A>G		intron	N/A	ENSP00000420191.1	F2Z307

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8489 AN: 152094 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0714

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0559 AC: 8510 AN: 152212 Hom.: 272 Cov.: 32 AF XY: 0.0544 AC XY: 4045 AN XY: 74418

African (AFR) AF: 0.0544 AC: 2259 AN: 41534

American (AMR) AF: 0.0565 AC: 864 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 281 AN: 3468

East Asian (EAS) AF: 0.0270 AC: 140 AN: 5186

South Asian (SAS) AF: 0.0619 AC: 298 AN: 4818

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0619 AC: 4208 AN: 67998

Other (OTH) AF: 0.0706 AC: 149 AN: 2110

Alfa AF: 0.0578 Hom.: 779

Bravo AF: 0.0582

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.0
DANN	Benign	0.65
PhyloP100		-0.60

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9267487;

hg19: chr6-31511350;