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NM_000157.4(GBA1):c.1246G>A (p.Gly416Ser) AND not provided

Germline classification:
Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:
Dec 28, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000723428.13

Allele description [Variation Report for NM_000157.4(GBA1):c.1246G>A (p.Gly416Ser)]

NM_000157.4(GBA1):c.1246G>A (p.Gly416Ser)

Genes:
LOC106627981:GBA recombination region [Gene]
GBA1:glucosylceramidase beta 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q22
Genomic location:
Preferred name:
NM_000157.4(GBA1):c.1246G>A (p.Gly416Ser)
Other names:
G377S
HGVS:
  • NC_000001.11:g.155235823C>T
  • NG_009783.1:g.13875G>A
  • NG_042867.1:g.2285C>T
  • NM_000157.3(GBA):c.1246G>A
  • NM_000157.4:c.1246G>AMANE SELECT
  • NM_001005741.3:c.1246G>A
  • NM_001005742.3:c.1246G>A
  • NM_001171811.2:c.985G>A
  • NM_001171812.2:c.1099G>A
  • NP_000148.2:p.Gly416Ser
  • NP_001005741.1:p.Gly416Ser
  • NP_001005742.1:p.Gly416Ser
  • NP_001165282.1:p.Gly329Ser
  • NP_001165283.1:p.Gly367Ser
  • NC_000001.10:g.155205614C>T
  • NM_000157.3(GBA):c.1246G>A
  • NM_000157.3:c.1246G>A
  • NM_001005741.2:c.1246G>A
  • NM_001005741.3:c.1246G>A
  • P04062:p.Gly416Ser
Protein change:
G329S; GLY377SER
Links:
UniProtKB: P04062#VAR_003303; OMIM: 606463.0040; dbSNP: rs121908311
NCBI 1000 Genomes Browser:
rs121908311
Molecular consequence:
  • NM_000157.4:c.1246G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005741.3:c.1246G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005742.3:c.1246G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171811.2:c.985G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001171812.2:c.1099G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000700355Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Pathogenic
(Apr 3, 2017)
germlineclinical testing

Citation Link,

SCV002018392Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Jun 24, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002125693Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 28, 2023)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV002578604GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Pathogenic
(Apr 5, 2022)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Use of denaturing gradient gel electrophoresis to identify mutant sequences in the beta-glucocerebrosidase gene.

Laubscher KH, Glew RH, Lee RE, Okinaka RT.

Hum Mutat. 1994;3(4):411-5. No abstract available.

PubMed [citation]
PMID:
8081401
See all PubMed Citations (9)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000700355.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From Revvity Omics, Revvity, SCV002018392.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002125693.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 416 of the GBA protein (p.Gly416Ser). This variant is present in population databases (rs121908311, gnomAD 0.003%). This missense change has been observed in individual(s) with Gaucher disease and/or Parkinson's disease (PMID: 8081401, 17395504, 20432762, 23430543, 25287185, 27632223, 29140481). It is commonly reported in individuals of Brazilian ancestry (PMID: 25287185). This variant is also known as p.Gly377Ser or G377S. ClinVar contains an entry for this variant (Variation ID: 4327). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GBA protein function. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV002578604.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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: 8081401, 25946768, 16981045, 17395504, 23430543, 25732996, 29140481, 27717005, 20432762, 21742527, 33176831, 31467847, 27632223, 25287185, 10757640, 12595585, 22429443)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024