6-32855081-G-T

Variant names:

• chr6-32855081-G-T
• rs4713600
• NM_002800.5:c.60+792G>T

Variant summary

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

The NM_002800.5(PSMB9):​c.60+792G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,976 control chromosomes in the GnomAD database, including 13,446 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 0.42 (13446 hom., cov: 32)
• Consequence: PSMB9 NM_002800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 53 publications found

Genes affected

PSMB9 (HGNC:9546): (proteasome 20S subunit beta 9) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. This gene is located in the class II region of the MHC (major histocompatibility complex). Expression of this gene is induced by gamma interferon and this gene product replaces catalytic subunit 1 (proteasome beta 6 subunit) in the immunoproteasome. Proteolytic processing is required to generate a mature subunit. [provided by RefSeq, Mar 2010]

PSMB9 Gene-Disease associations (from GenCC):

• proteasome-associated autoinflammatory syndrome 3

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002800.5. 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
	PSMB9	NM_002800.5	MANE Select	c.60+792G>T		intron	N/A	NP_002791.1	P28065-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB9	ENST00000374859.3	TSL:1 MANE Select	c.60+792G>T		intron	N/A	ENSP00000363993.2	P28065-1
	PSMB9	ENST00000892972.1		c.60+792G>T		intron	N/A	ENSP00000563031.1
	PSMB9	ENST00000395330.6	TSL:3	c.-9-1057G>T		intron	N/A	ENSP00000378739.1	A2ACR1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63535 AN: 151858 Hom.: 13427 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.418 AC: 63599 AN: 151976 Hom.: 13446 Cov.: 32 AF XY: 0.415 AC XY: 30797 AN XY: 74278

African (AFR) AF: 0.442 AC: 18315 AN: 41434

American (AMR) AF: 0.414 AC: 6324 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1551 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1918 AN: 5172

South Asian (SAS) AF: 0.387 AC: 1864 AN: 4818

European-Finnish (FIN) AF: 0.370 AC: 3899 AN: 10532

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28325 AN: 67956

Other (OTH) AF: 0.428 AC: 900 AN: 2102

Alfa AF: 0.418 Hom.: 58890

Bravo AF: 0.421

Asia WGS AF: 0.423 AC: 1472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.58
PhyloP100		-0.60
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: rs4713600; hg19: chr6-32822858;