VCV000042466.39 - ClinVar

NM_000169.3(GLA):c.978G>A (p.Lys326=)

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.

(14)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000169.3(GLA):c.978G>A (p.Lys326=)

Variation ID: 42466 Accession: VCV000042466.39

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq22.1 X: 101398391 (GRCh38) [ NCBI UCSC ] X: 100653379 (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	Oct 2, 2016	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000169.3:c.978G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000160.1:p.Lys326=	synonymous
NM_001199973.2:c.300+2934C>T		intron variant
NM_001199974.2:c.177+6569C>T		intron variant
NM_001406747.1:c.1101G>A	NP_001393676.1:p.Lys367=	synonymous
NM_001406748.1:c.978G>A	NP_001393677.1:p.Lys326=	synonymous
NR_164783.1:n.1057G>A		non-coding transcript variant
NR_176252.1:n.908G>A		non-coding transcript variant
NR_176253.1:n.1115G>A		non-coding transcript variant
NC_000023.11:g.101398391C>T
NC_000023.10:g.100653379C>T
NG_007119.1:g.14573G>A
LRG_672:g.14573G>A
LRG_672t1:c.978G>A	LRG_672p1:p.Lys326=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000023.11:101398390: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.

0.00079 (T)

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

The Genome Aggregation Database (gnomAD), exomes 0.00027

Exome Aggregation Consortium (ExAC) 0.00033

1000 Genomes Project 30x 0.00062

1000 Genomes Project 0.00079

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00095

The Genome Aggregation Database (gnomAD) 0.00100

Trans-Omics for Precision Medicine (TOPMed) 0.00120

Links

dbSNP: rs151195362 ClinGen: CA022243 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.
GLA		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	7	1257
RPL36A-HNRNPH2	-	-	-	GRCh38 GRCh37	-	1293

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 specified	Benign/Likely benign (5)	criteria provided, multiple submitters, no conflicts	Mar 11, 2021	RCV000035316.23
Fabry disease	Benign (3)	criteria provided, multiple submitters, no conflicts	Jan 29, 2024	RCV000226702.20
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	Jan 5, 2016	RCV000618274.4
not provided	Benign/Likely benign (5)	criteria provided, multiple submitters, no conflicts	Aug 1, 2024	RCV001659952.6

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.
Benign (Apr 18, 2015)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000058964.5 First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016	Comment: p.Lys326Lys in exon 6 of GLA: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, … (more) p.Lys326Lys in exon 6 of GLA: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.3% (24/8490) of Afri can chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; rs151195362). (less) Number of individuals with the variant: 3
Benign (Apr 22, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000202796.7 First in ClinVar: Jan 31, 2015 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GLA Number of individuals with the variant: 2 Sex: mixed
Benign (Jan 29, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Fabry disease Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000283693.11 First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024
Likely benign (Mar 11, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV001519437.1 First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021
Likely benign (Jan 05, 2016)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000736814.5 First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000302838.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Dec 16, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Fabry disease Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV001356729.1 First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001881827.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021
Likely benign (Aug 01, 2024)	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: SCV005331030.2 First in ClinVar: Oct 08, 2024 Last updated: Oct 20, 2024	Comment: GLA: BP4, BS2 Number of individuals with the variant: 1
Benign (Jul 15, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Fabry disease Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002054328.1 First in ClinVar: Jan 12, 2022 Last updated: Jan 12, 2022
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001926436.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001926168.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001963342.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001974782.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
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Comment:

p.Lys326Lys in exon 6 of GLA: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.3% (24/8490) of Afri can chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; rs151195362).

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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=GLA	-	-	-	-

Text-mined citations for rs151195362 ...

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_000169.3(GLA):c.978G>A (p.Lys326=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs151195362 ...