VCV003027432.2 - ClinVar

NM_005861.4(STUB1):c.728C>T (p.Pro243Leu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005861.4(STUB1):c.728C>T (p.Pro243Leu)

Variation ID: 3027432 Accession: VCV003027432.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16p13.3 16: 682223 (GRCh38) [ NCBI UCSC ] 16: 732223 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 11, 2024	Oct 8, 2024	Sep 20, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001005920.4:c.*571G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_005861.4:c.728C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005852.2:p.Pro243Leu	missense
NM_001293197.2:c.512C>T	NP_001280126.1:p.Pro171Leu	missense
NM_001323918.3:c.*605G>A		3 prime UTR
NM_001323919.3:c.*571G>A		3 prime UTR
NM_001323920.3:c.*571G>A		3 prime UTR
NM_001323922.3:c.*605G>A		3 prime UTR
NM_005861.2:c.728C>T
NR_136650.3:n.1464G>A		non-coding transcript variant
NR_136651.3:n.1469G>A		non-coding transcript variant
NR_136652.3:n.1379G>A		non-coding transcript variant
NC_000016.10:g.682223C>T
NC_000016.9:g.732223C>T
NG_034141.1:g.7113C>T
NG_132623.1:g.547C>T

... more HGVS ... less HGVS

Protein change

P171L, P243L

Other names

Canonical SPDI

NC_000016.10:682222:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
JMJD8	-	-	-	GRCh38 GRCh37	38	233
STUB1		-	-	GRCh38 GRCh37	79	264

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Spinocerebellar ataxia 48	Uncertain significance (1)	criteria provided, single submitter	May 31, 2023	RCV003887824.1
not provided	Likely pathogenic (1)	criteria provided, single submitter	Sep 20, 2023	RCV004721235.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (May 31, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Spinocerebellar ataxia 48 Affected status: yes Allele origin: germline	Human Genetics Bochum, Ruhr University Bochum Accession: SCV004704501.1 First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024	Comment: ACMG criteria used to clasify this variant: PM1, PP3_MOD, PM2_SUP Clinical Features: Gait ataxia (present) , Dysarthria (present)
Likely pathogenic (Sep 20, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV005327912.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: Published functional studies demonstrate a damaging effect on folding of the entire U box domain, thereby affecting and reducing the E3 activity of CHIP (Saito … (more) Published functional studies demonstrate a damaging effect on folding of the entire U box domain, thereby affecting and reducing the E3 activity of CHIP (Saito et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36476347, 28193273, 36422518, 32713943, 34906452) (less)

Comment:

Published functional studies demonstrate a damaging effect on folding of the entire U box domain, thereby affecting and reducing the E3 activity of CHIP (Saito et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36476347, 28193273, 36422518, 32713943, 34906452)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_005861.4(STUB1):c.728C>T (p.Pro243Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...