U.S. flag

An official website of the United States government

NM_003334.4(UBA1):c.167C>T (p.Ser56Phe) AND VEXAS syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 4, 2021
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001726682.1

Allele description [Variation Report for NM_003334.4(UBA1):c.167C>T (p.Ser56Phe)]

NM_003334.4(UBA1):c.167C>T (p.Ser56Phe)

Genes:
LOC126863253:CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:47057593-47058792 [Gene]
UBA1:ubiquitin like modifier activating enzyme 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.3
Genomic location:
Preferred name:
NM_003334.4(UBA1):c.167C>T (p.Ser56Phe)
Other names:
S56F
HGVS:
  • NC_000023.11:g.47199097C>T
  • NG_009161.1:g.13298C>T
  • NM_003334.4:c.167C>TMANE SELECT
  • NM_153280.3:c.167C>T
  • NP_003325.2:p.Ser56Phe
  • NP_695012.1:p.Ser56Phe
  • NC_000023.10:g.47058496C>T
Protein change:
SER56PHE
Links:
OMIM: 314370.0007; dbSNP: rs2147250370
NCBI 1000 Genomes Browser:
rs2147250370
Molecular consequence:
  • NM_003334.4:c.167C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153280.3:c.167C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
VEXAS syndrome
Identifiers:
MONDO: MONDO:0026777; MedGen: C5435753; OMIM: 301054

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001960898OMIM
no assertion criteria provided
Pathogenic
(Oct 4, 2021) 		somaticliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Novel somatic mutations in UBA1 as a cause of VEXAS syndrome.

Poulter JA, Collins JC, Cargo C, De Tute RM, Evans P, Ospina Cardona D, Bowen DT, Cunnington JR, Baguley E, Quinn M, Green M, McGonagle D, Beck DB, Werner A, Savic S.

Blood. 2021 Jul 1;137(26):3676-3681. doi: 10.1182/blood.2020010286. No abstract available.

PubMed [citation]
PMID:
33690815
PMCID:
PMC8462400

Details of each submission

From OMIM, SCV001960898.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a man (patient 9) with VEXAS syndrome (VEXAS; 301054), Poulter et al. (2021) identified a somatic c.167C-T transition (c.167C-T, NM_153280) in the UBA1 gene, resulting in a ser56-to-phe (S56P) substitution. The mutation was identified by Sanger sequencing of the UBA1 gene and was not present in the gnomAD database. Testing in patient blood cells showed that myeloid cells predominantly had the mutant S56P allele, whereas B- and T-cell lineage populations predominantly were wildtype. The mutation did not affect UBA1 cellular localization or result in isoform expression abnormalities in HEK293 cells transfected with the mutant transcript. Poulter et al. (2021) demonstrated that the mutation resulted in temperature-dependent impairment of UBA1 catalytic activity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticnot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024