rs1553209362

Variant names:

• chr1-151401295-CGACTTAGTA-C
• rs1553209362
• NM_002796.3:c.636_644delCTTAGTAGA

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_002796.3(PSMB4):​c.636_644delCTTAGTAGA​(p.Asp212_Val214del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMB4 NM_002796.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.77
• Publications: 0 publications found

Genes affected

PSMB4 (HGNC:9541): (proteasome 20S subunit beta 4) 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. [provided by RefSeq, Jul 2008]

PSMB4 Gene-Disease associations (from GenCC):

• proteasome-associated autoinflammatory syndrome 3

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002796.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 1-151401295-CGACTTAGTA-C is Pathogenic according to our data. Variant chr1-151401295-CGACTTAGTA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 548955.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002796.3. 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
	PSMB4	NM_002796.3	MANE Select	c.636_644delCTTAGTAGA	p.Asp212_Val214del	disruptive_inframe_deletion	Exon 5 of 7	NP_002787.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMB4	ENST00000290541.7	TSL:1 MANE Select	c.636_644delCTTAGTAGA	p.Asp212_Val214del	disruptive_inframe_deletion	Exon 5 of 7	ENSP00000290541.6	P28070
	PSMB4	ENST00000933663.1		c.429_437delCTTAGTAGA	p.Asp143_Val145del	disruptive_inframe_deletion	Exon 4 of 6	ENSP00000603722.1
	PSMB4	ENST00000933662.1		c.577-244_577-236delCTTAGTAGA		intron	N/A	ENSP00000603721.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Proteasome-associated autoinflammatory syndrome 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.8
Mutation Taster		=21/179	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553209362; hg19: chr1-151373771;