6-32857602-A-T

Variant names:

• chr6-32857602-A-T
• rs2071476
• NM_002800.5:c.260+208A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002800.5(PSMB9):​c.260+208A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 415,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PSMB9 NM_002800.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSMB9	NM_002800.5	c.260+208A>T		intron_variant	Intron 3 of 5	ENST00000374859.3	NP_002791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSMB9	ENST00000374859.3	c.260+208A>T		intron_variant	Intron 3 of 5	1	NM_002800.5	ENSP00000363993.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000482 AC: 2 AN: 415102 Hom.: 0 Cov.: 5 AF XY: 0.00000931 AC XY: 2 AN XY: 214736

African (AFR) AF: 0.00 AC: 0 AN: 11404

American (AMR) AF: 0.00 AC: 0 AN: 13976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12492

East Asian (EAS) AF: 0.00 AC: 0 AN: 28540

South Asian (SAS) AF: 0.00 AC: 0 AN: 30338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1850

European-Non Finnish (NFE) AF: 0.00000753 AC: 2 AN: 265572

Other (OTH) AF: 0.00 AC: 0 AN: 23966

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.91
DANN	Benign	0.61
PhyloP100		-0.20

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: rs2071476; hg19: chr6-32825379;