VCV000597184.34 - ClinVar

NM_000157.4(GBA1):c.928A>G (p.Ser310Gly)

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.

(5)

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
Pathogenic(1); Likely pathogenic(3); 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_000157.4(GBA1):c.928A>G (p.Ser310Gly)

Variation ID: 597184 Accession: VCV000597184.34

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q22 1: 155237412 (GRCh38) [ NCBI UCSC ] 1: 155207203 (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	Dec 16, 2018	Oct 20, 2024	Dec 19, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000157.4:c.928A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000148.2:p.Ser310Gly	missense
NM_001005741.3:c.928A>G	NP_001005741.1:p.Ser310Gly	missense
NM_001005742.3:c.928A>G	NP_001005742.1:p.Ser310Gly	missense
NM_001171811.2:c.667A>G	NP_001165282.1:p.Ser223Gly	missense
NM_001171812.2:c.781A>G	NP_001165283.1:p.Ser261Gly	missense
NC_000001.11:g.155237412T>C
NC_000001.10:g.155207203T>C
NG_009783.1:g.12286A>G
NG_042867.1:g.3874T>C

... more HGVS ... less HGVS

Protein change

S310G, S261G, S223G

Other names

Canonical SPDI

NC_000001.11:155237411:T:C

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.

The Genome Aggregation Database (gnomAD) 0.00004

Trans-Omics for Precision Medicine (TOPMed) 0.00004

Links

dbSNP: rs1057942 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.
GBA1		-	-	GRCh38 GRCh38 GRCh37	32	405
LOC106627981	-	-	-	GRCh38 GRCh38	-	359

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.
not provided	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	Dec 19, 2023	RCV000733225.27
Gaucher disease perinatal lethal Gaucher disease type I Gaucher disease type II Gaucher disease type III Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome Lewy body dementia Parkinson disease, late-onset	Likely pathogenic (1)	criteria provided, single submitter	Sep 26, 2021	RCV002499368.2
Parkinson disease, late-onset	Pathogenic (1)	criteria provided, single submitter	Jan 25, 2023	RCV003336163.4

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.
Likely pathogenic (Jun 04, 2018)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000861263.1 First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GBA Number of individuals with the variant: 1 Sex: mixed
Likely pathogenic (Sep 26, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lewy body dementia Parkinson disease, late-onset Gaucher disease type I Gaucher disease type II Gaucher disease type III Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome Gaucher disease perinatal lethal Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002813242.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Jan 25, 2023)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Parkinson disease, late-onset (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV004045946.1 First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023	Number of individuals with the variant: 1 Clinical Features: Sensory neuropathy (present) , Spina bifida occulta (present) , Dystonic disorder (present) , Myopathy (present) , Parkinsonian disorder (present)
Uncertain significance (Dec 19, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV005324976.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Comment: Reported as heterozygous in multiple individuals with late onset Parkinson disease and early onset Parkinson disease and also seen in controls (PMID: 33281709, 18541817, 21779299, … (more) Reported as heterozygous in multiple individuals with late onset Parkinson disease and early onset Parkinson disease and also seen in controls (PMID: 33281709, 18541817, 21779299, 34779914, 35861376, 37658046, 36872856, 37312046, 32613234); Reported previously in a patient with progressive supranuclear palsy and seen in one control; no further clinical information was provided (PMID: 35842134); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 18541817, 33583590, 32618053, 34134921, 32165122, 37312046, 34779914, 35861376, 36872856, 37658046, 21779299, 36683633, 33281709, 33383316, 36637080, 34867278, 35842134, 32613234) (less)
Likely pathogenic (Oct 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001247922.26 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Comment: GBA1: PM2, PM3, PM5 Number of individuals with the variant: 3

Comment:

Reported as heterozygous in multiple individuals with late onset Parkinson disease and early onset Parkinson disease and also seen in controls (PMID: 33281709, 18541817, 21779299, 34779914, 35861376, 37658046, 36872856, 37312046, 32613234); Reported previously in a patient with progressive supranuclear palsy and seen in one control; no further clinical information was provided (PMID: 35842134); In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 18541817, 33583590, 32618053, 34134921, 32165122, 37312046, 34779914, 35861376, 36872856, 37658046, 21779299, 36683633, 33281709, 33383316, 36637080, 34867278, 35842134, 32613234)

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

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GBA	-	-	-	-

Text-mined citations for rs1057942 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_000157.4(GBA1):c.928A>G (p.Ser310Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1057942 ...