NM_148919.4(PSMB8):c.574C>T (p.Arg192Trp) AND Proteosome-associated autoinflammatory syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 7, 2023
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:: RCV003763784.1

Allele description

NM_148919.4(PSMB8):c.574C>T (p.Arg192Trp)

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.574C>T (p.Arg192Trp)

HGVS:

NC_000006.12:g.32841699G>A
NG_009793.3:g.2072C>T
NG_028165.1:g.8237C>T
NM_004159.5:c.562C>T
NM_148919.4:c.574C>TMANE SELECT
NP_004150.1:p.Arg188Trp
NP_683720.2:p.Arg192Trp
LRG_1328t1:c.574C>T
LRG_1328t2:c.562C>T
LRG_1328:g.8237C>T
LRG_1328p1:p.Arg192Trp
LRG_1328p2:p.Arg188Trp
NC_000006.11:g.32809476G>A
NM_148919.3:c.574C>T

Protein change:

R188W

Links:

dbSNP: rs752232985

NCBI 1000 Genomes Browser:

rs752232985

Molecular consequence:

NM_004159.5:c.562C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_148919.4:c.574C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001226991	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001226991

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 7, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001226991.5

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 192 of the PSMB8 protein (p.Arg192Trp). This variant is present in population databases (rs752232985, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PSMB8-related conditions. ClinVar contains an entry for this variant (Variation ID: 856695). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PSMB8 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 16, 2024

ClinVar

Relating variation to medicine