NM_005861.4(STUB1):c.433A>C (p.Lys145Gln) AND Inborn genetic diseases

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 1, 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:: RCV002517140.9

Allele description [Variation Report for NM_005861.4(STUB1):c.433A>C (p.Lys145Gln)]

NM_005861.4(STUB1):c.433A>C (p.Lys145Gln)

Gene:

STUB1:STIP1 homology and U-box containing protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_005861.4(STUB1):c.433A>C (p.Lys145Gln)

Other names:

STUB1, LYS145GLN (rs146251364)

HGVS:

NC_000016.10:g.681512A>C
NG_034141.1:g.6402A>C
NM_001293197.2:c.217A>C
NM_005861.4:c.433A>CMANE SELECT
NP_001280126.1:p.Lys73Gln
NP_005852.2:p.Lys145Gln
NC_000016.9:g.731512A>C
NM_005861.2:c.433A>C
Q9UNE7:p.Lys145Gln

Protein change:

K145Q; LYS145GLN

Links:

UniProtKB: Q9UNE7#VAR_072350; OMIM: 607207.0013; dbSNP: rs146251364

NCBI 1000 Genomes Browser:

rs146251364

Molecular consequence:

NM_001293197.2:c.217A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005861.4:c.433A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003539602	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 1, 2023)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 24719489, 28193273, 28396517, 28444220, 29317501, 29915382, 32367277, 33097556, 33417001, 34234304 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003539602

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 1, 2023)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

Citation Link

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

Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations.

Depondt C, Donatello S, Simonis N, Rai M, van Heurck R, Abramowicz M, D'Hooghe M, Pandolfo M.

Neurology. 2014 May 13;82(19):1749-50. doi: 10.1212/WNL.0000000000000416. Epub 2014 Apr 9.

PubMed [citation]

PMID:: 24719489

STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations.

Hayer SN, Deconinck T, Bender B, Smets K, Züchner S, Reich S, Schöls L, Schüle R, De Jonghe P, Baets J, Synofzik M.

Orphanet J Rare Dis. 2017 Feb 13;12(1):31. doi: 10.1186/s13023-017-0580-x.

PubMed [citation]

PMID:: 28193273
PMCID:: PMC5307643

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV003539602.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The c.433A>C (p.K145Q) alteration is located in exon 3 (coding exon 3) of the STUB1 gene. This alteration results from a A to C substitution at nucleotide position 433, causing the lysine (K) at amino acid position 145 to be replaced by a glutamine (Q). This alteration has been reported in multiple individuals with features of STUB1-related spinocerebellar ataxia (Benkirane, 2021; Coutelier, 2017; Sun, 2019). Functional analysis demonstrated reduced CHIP protein levels in cortical neurons derived from patient fibroblasts containing c.433A>C (p.K145Q) and c.728C>T (p.P243L) in the compound heterozygote state (Schuster, 2020). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

#	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: Jun 2, 2024

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