VCV002627744.1 - ClinVar

NM_000157.4(GBA1):c.907C>A (p.Leu303Ile)

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.

(1)

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.

Uncertain significance

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000157.4(GBA1):c.907C>A (p.Leu303Ile)

Variation ID: 2627744 Accession: VCV002627744.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q22 1: 155207224 (GRCh37) [ NCBI UCSC ] 1: 155237433 (GRCh38) [ 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	Nov 11, 2023	Nov 11, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000157.4:c.907C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000148.2:p.Leu303Ile	missense
NM_001005741.3:c.907C>A	NP_001005741.1:p.Leu303Ile	missense
NM_001005742.3:c.907C>A	NP_001005742.1:p.Leu303Ile	missense
NM_001171811.2:c.646C>A	NP_001165282.1:p.Leu216Ile	missense
NM_001171812.2:c.760C>A	NP_001165283.1:p.Leu254Ile	missense
NC_000001.11:g.155237433G>T
NC_000001.10:g.155207224G>T
NG_009783.1:g.12265C>A
NG_042867.1:g.3895G>T

... more HGVS ... less HGVS

Protein change

L216I, L254I, L303I

Other names

Canonical SPDI

NC_000001.11:155237432:G: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.
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.
Gaucher disease type I	Uncertain significance (1)	no assertion criteria provided	-	RCV003389033.2

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 (-)	no assertion criteria provided Method: literature only	Gaucher disease type I Affected status: unknown Allele origin: biparental	Department of Traditional Chinese Medicine, Fujian Provincial Hospital Accession: SCV004100809.1 First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023	Publications: DOI: 10.1038/jhg.2014.110 DOI: 10.1038/jhg.2014.110 DOI: 10.1016/j.scr.2018.101373 DOI: 10.1016/j.scr.2018.101373 DOI: 10.1002/mds.28195 DOI: 10.1002/mds.28195 Comment: A patient with combined splenomegaly and thrombocytopenia was genetically tested for mutant GBA (NM_001005741): c.907C>A (p.Leu303Ile), a missense mutation in exon 8, for which impairment … (more) A patient with combined splenomegaly and thrombocytopenia was genetically tested for mutant GBA (NM_001005741): c.907C>A (p.Leu303Ile), a missense mutation in exon 8, for which impairment of protein function is predicted by:SIFT: Deleterious; Polyphen2: Possibly damaging; MutationTaster: disease causing, and according to the ACMG guidelines, this mutation site meets the following criteria: PM1: Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation; PM2: Absent from controls (or at extremely low frequency if recessive) in the Exome Sequencing Project, 1000 Genomes or ExAC; and PP3: Multiple lines of computational evidence supporting a deleterious effect on the gene or gene product (conservation, evolutionary, spatial). product (conservation, evolutionary, splicing impact, etc). The mutation is considered to be of "uncertain significance". (less)

Comment:

A patient with combined splenomegaly and thrombocytopenia was genetically tested for mutant GBA (NM_001005741): c.907C>A (p.Leu303Ile), a missense mutation in exon 8, for which impairment of protein function is predicted by:SIFT: Deleterious; Polyphen2: Possibly damaging; MutationTaster: disease causing, and according to the ACMG guidelines, this mutation site meets the following criteria: PM1: Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation; PM2: Absent from controls (or at extremely low frequency if recessive) in the Exome Sequencing Project, 1000 Genomes or ExAC; and PP3: Multiple lines of computational evidence supporting a deleterious effect on the gene or gene product (conservation, evolutionary, spatial). product (conservation, evolutionary, splicing impact, etc). The mutation is considered to be of "uncertain significance".

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
-	-	-	-	DOI: 10.1002/mds.28195
-	-	-	-	DOI: 10.1016/j.scr.2018.101373
-	-	-	-	DOI: 10.1038/jhg.2014.110

Text-mined citations for this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_000157.4(GBA1):c.907C>A (p.Leu303Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...