rs1351383

Variant names:

• chr6-32854492-A-C
• rs1351383
• NM_002800.5:c.60+203A>C

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+203A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,924 control chromosomes in the GnomAD database, including 13,996 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 0.43 (13996 hom., cov: 31)
• Consequence: PSMB9 NM_002800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 38 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB9	NM_002800.5	MANE Select	c.60+203A>C		intron	N/A	NP_002791.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB9	ENST00000374859.3	TSL:1 MANE Select	c.60+203A>C		intron	N/A	ENSP00000363993.2
	PSMB9	ENST00000395330.6	TSL:3	c.-9-1646A>C		intron	N/A	ENSP00000378739.1
	PSMB9	ENST00000414474.5	TSL:5	c.-9-1646A>C		intron	N/A	ENSP00000394363.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64774 AN: 151806 Hom.: 13974 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.427 AC: 64842 AN: 151924 Hom.: 13996 Cov.: 31 AF XY: 0.423 AC XY: 31408 AN XY: 74242

African (AFR) AF: 0.469 AC: 19416 AN: 41428

American (AMR) AF: 0.418 AC: 6387 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1927 AN: 5172

South Asian (SAS) AF: 0.405 AC: 1952 AN: 4820

European-Finnish (FIN) AF: 0.369 AC: 3883 AN: 10534

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

European-Non Finnish (NFE) AF: 0.417 AC: 28310 AN: 67914

Other (OTH) AF: 0.433 AC: 915 AN: 2114

Alfa AF: 0.424 Hom.: 21943

Bravo AF: 0.430

Asia WGS AF: 0.451 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.37
PhyloP100		-1.2
PromoterAI		-0.025	Neutral
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: rs1351383; hg19: chr6-32822269;