NM_148919.4(PSMB8):c.224C>T (p.Thr75Met) AND PSMB8-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 13, 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:: RCV003411802.4

Allele description [Variation Report for NM_148919.4(PSMB8):c.224C>T (p.Thr75Met)]

NM_148919.4(PSMB8):c.224C>T (p.Thr75Met)

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.224C>T (p.Thr75Met)

HGVS:

NC_000006.12:g.32843013G>A
NG_009793.3:g.758C>T
NG_028165.1:g.6923C>T
NM_004159.5:c.212C>T
NM_148919.4:c.224C>TMANE SELECT
NP_004150.1:p.Thr71Met
NP_683720.2:p.Thr75Met
LRG_1328t1:c.224C>T
LRG_1328t2:c.212C>T
LRG_1328:g.6923C>T
LRG_1328p1:p.Thr75Met
LRG_1328p2:p.Thr71Met
NC_000006.11:g.32810790G>A
NM_148919.3:c.224C>T

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

T71M; THR75MET

Links:

OMIM: 177046.0001; dbSNP: rs748082671

NCBI 1000 Genomes Browser:

rs748082671

Molecular consequence:

NM_004159.5:c.212C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_148919.4:c.224C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PSMB8-related disorder
Synonyms:: PSMB8-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004112984	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 13, 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

SCV004112984

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 13, 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004112984.1

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

Description

The PSMB8 c.224C>T variant is predicted to result in the amino acid substitution p.Thr75Met. This variant has been reported in patients with joint contractures, muscle atrophy, microcytic anemia, and panniculitis induced lipodystrophy syndrome (JMP) and CANDLE syndrome (Agarwal et al. 2010. PubMed ID: 21129723; Brehm et al. 2015. PubMed ID: 26524591; Liu et al. 2012. PubMed ID: 21953331). Functional studies indicate the c.224C>T (p.Thr75Met) variant impairs proteosomal activity (Agarwal et al. 2010. PubMed ID: 21129723). This variant is interpreted as pathogenic.

#	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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