NM_005861.4(STUB1):c.427AAG[2] (p.Lys145del) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Apr 30, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001590241.12

Allele description [Variation Report for NM_005861.4(STUB1):c.427AAG[2] (p.Lys145del)]

NM_005861.4(STUB1):c.427AAG[2] (p.Lys145del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_005861.4(STUB1):c.427AAG[2] (p.Lys145del)

HGVS:

NC_000016.10:g.681506AAG[2]
NG_034141.1:g.6396AAG[2]
NM_001293197.2:c.211AAG[2]
NM_005861.4:c.427AAG[2]MANE SELECT
NM_005861.4:c.433_435del
NP_001280126.1:p.Lys73del
NP_005852.2:p.Lys145del
NC_000016.9:g.731505_731507del
NC_000016.9:g.731506AAG[2]
NM_005861.2:c.433_435del
NM_005861.4:c.433_435delMANE SELECT
NM_005861.4:c.433_435delAAGMANE SELECT

Protein change:

K145del

Links:

dbSNP: rs779647632

NCBI 1000 Genomes Browser:

rs779647632

Molecular consequence:

NM_001293197.2:c.211AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_005861.4:c.427AAG[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001826031	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 30, 2024)	germline	clinical testing	Citation Link,
SCV002034927	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002037984	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV003244295	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32713943, 34663476, 28492532

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical, neuropathological, and genetic characterization of STUB1 variants in cerebellar ataxias: a frequent cause of predominant cognitive impairment.

Roux T, Barbier M, Papin M, Davoine CS, Sayah S, Coarelli G, Charles P, Marelli C, Parodi L, Tranchant C, Goizet C, Klebe S, Lohmann E, Van Maldergem L, van Broeckhoven C, Coutelier M, Tesson C, Stevanin G, Duyckaerts C, Brice A, Durr A; SPATAX network..

Genet Med. 2020 Nov;22(11):1851-1862. doi: 10.1038/s41436-020-0899-x. Epub 2020 Jul 27. Erratum in: Genet Med. 2021 Oct;23(10):2021. doi: 10.1038/s41436-020-01064-y.

PubMed [citation]

PMID:: 32713943

Genetic spectrum and clinical features in a cohort of Chinese patients with autosomal recessive cerebellar ataxias.

Cheng HL, Shao YR, Dong Y, Dong HL, Yang L, Ma Y, Shen Y, Wu ZY.

Transl Neurodegener. 2021 Oct 18;10(1):40. doi: 10.1186/s40035-021-00264-z.

PubMed [citation]

PMID:: 34663476
PMCID:: PMC8522248

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV001826031.3

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

Description

In-frame deletion of 1 amino acid in a non-repeat region; Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33057194, 35982159, 34663476, 34906452)

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV002034927.1

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

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV002037984.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003244295.2

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

Description

This variant, c.433_435del, results in the deletion of 1 amino acid(s) of the STUB1 protein (p.Lys145del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs779647632, gnomAD 0.0009%). This variant has been observed in individual(s) with clinical features of STUB1-related conditions (PMID: 32713943, 34663476). This variant is also known as c.426_428del; p.K143del. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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: Nov 3, 2024

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