NM_148919.4(PSMB8):c.405C>A (p.Cys135Ter) AND Proteosome-associated autoinflammatory syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 5, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003595858.2

Allele description [Variation Report for NM_148919.4(PSMB8):c.405C>A (p.Cys135Ter)]

NM_148919.4(PSMB8):c.405C>A (p.Cys135Ter)

Gene:

PSMB8:proteasome 20S subunit beta 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.32

Genomic location:

Preferred name:

NM_148919.4(PSMB8):c.405C>A (p.Cys135Ter)

HGVS:

NC_000006.12:g.32842674G>T
NG_009793.3:g.1097C>A
NG_028165.1:g.7262C>A
NM_004159.5:c.393C>A
NM_148919.4:c.405C>AMANE SELECT
NP_004150.1:p.Cys131Ter
NP_683720.2:p.Cys135Ter
LRG_1328t1:c.405C>A
LRG_1328t2:c.393C>A
LRG_1328:g.7262C>A
LRG_1328p1:p.Cys135Ter
LRG_1328p2:p.Cys131Ter
NC_000006.11:g.32810451G>T
NM_148919.3:c.405C>A

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

C131*; CYS135TER

Links:

OMIM: 177046.0004; dbSNP: rs146254972

NCBI 1000 Genomes Browser:

rs146254972

Molecular consequence:

NM_004159.5:c.393C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_148919.4:c.405C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Proteosome-associated autoinflammatory syndrome
Synonyms:: Proteasome-associated autoinflammatory syndrome
Identifiers:: MONDO: MONDO:0009726; MedGen: C1850568; OMIM: PS256040

Recent activity

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Chain A, PYRROLIDONE CARBOXYL PEPTIDASE
Chain A, PYRROLIDONE CARBOXYL PEPTIDASE
gi|13787021|pdb|1IOF|A

Protein
microtubule-associated protein 2 isoform 16 [Homo sapiens]
microtubule-associated protein 2 isoform 16 [Homo sapiens]
gi|1770726283|ref|NP_001362486.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002247274	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 5, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21953331, 26524591, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247274

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 5, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in proteasome subunit β type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity.

Liu Y, Ramot Y, Torrelo A, Paller AS, Si N, Babay S, Kim PW, Sheikh A, Lee CC, Chen Y, Vera A, Zhang X, Goldbach-Mansky R, Zlotogorski A.

Arthritis Rheum. 2012 Mar;64(3):895-907. doi: 10.1002/art.33368.

PubMed [citation]

PMID:: 21953331
PMCID:: PMC3278554

Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production.

Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q, Montealegre G, Biancotto A, Reinhardt A, Almeida de Jesus A, Pelletier M, Tsai WL, Remmers EF, Kardava L, Hill S, Kim H, Lachmann HJ, Megarbane A, Chae JJ, Brady J, Castillo RD, Brown D, et al.

J Clin Invest. 2015 Nov 2;125(11):4196-211. doi: 10.1172/JCI81260. Epub 2015 Oct 20. Erratum in: J Clin Invest. 2016 Feb;126(2):795. doi: 10.1172/JCI86020. Rother, Kristina [corrected to Rother, Kristina I].

PubMed [citation]

PMID:: 26524591
PMCID:: PMC4639987

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002247274.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has been observed in individual(s) with CANDLE syndrome (PMID: 21953331). ClinVar contains an entry for this variant (Variation ID: 29862). For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant alters PSMB8 gene expression (PMID: 26524591). This variant is present in population databases (rs146254972, ExAC 0.007%). This sequence change creates a premature translational stop signal (p.Cys135*) in the PSMB8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PSMB8 are known to be pathogenic (PMID: 26524591).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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