ClinVar Genomic variation as it relates to human health
NM_000023.4(SGCA):c.115A>G (p.Thr39Ala)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000023.4(SGCA):c.115A>G (p.Thr39Ala)
Variation ID: 811177 Accession: VCV000811177.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.33 17: 50167445 (GRCh38) [ NCBI UCSC ] 17: 48244806 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 10, 2020 May 1, 2024 Nov 21, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000023.4:c.115A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000014.1:p.Thr39Ala missense NM_001135697.3:c.115A>G NP_001129169.1:p.Thr39Ala missense NR_135553.2:n.151A>G non-coding transcript variant NC_000017.11:g.50167445A>G NC_000017.10:g.48244806A>G NG_008889.1:g.6441A>G LRG_203:g.6441A>G LRG_203t1:c.115A>G - Protein change
- T39A
- Other names
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- Canonical SPDI
- NC_000017.11:50167444:A:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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0.00020 (G)
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00004
Exome Aggregation Consortium (ExAC) 0.00005
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00022
The Genome Aggregation Database (gnomAD) 0.00026
1000 Genomes Project 30x 0.00031
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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. |
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SGCA | - | - |
GRCh38 GRCh37 |
741 | 764 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
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Feb 8, 2023 | RCV001000875.17 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 14, 2021 | RCV002549144.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 21, 2023 | RCV003479261.1 |
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
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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
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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. |
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Uncertain significance
(Oct 26, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157956.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The SGCA c.115A>G; p.Thr39Ala variant (rs540292629), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in … (more)
The SGCA c.115A>G; p.Thr39Ala variant (rs540292629), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the African population with an allele frequency of 0.063% (15/23,996 alleles) in the Genome Aggregation Database. The threonine at codon 39 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Thr39Ala variant is uncertain at this time. (less)
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Uncertain significance
(Apr 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001419902.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 39 of the SGCA protein (p.Thr39Ala). … (more)
This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 39 of the SGCA protein (p.Thr39Ala). This variant is present in population databases (rs540292629, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SGCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 811177). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Feb 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV003931631.1
First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023 |
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Uncertain significance
(Nov 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004223001.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
Variant summary: SGCA c.115A>G (p.Thr39Ala) results in a non-conservative amino acid change located in the Dystroglycan-type cadherin-like (IPR006644) of the encoded protein sequence. Three of … (more)
Variant summary: SGCA c.115A>G (p.Thr39Ala) results in a non-conservative amino acid change located in the Dystroglycan-type cadherin-like (IPR006644) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251454 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.115A>G in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Nov 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003827590.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Jul 14, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003535172.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.115A>G (p.T39A) alteration is located in exon 2 (coding exon 2) of the SGCA gene. This alteration results from a A to G substitution … (more)
The c.115A>G (p.T39A) alteration is located in exon 2 (coding exon 2) of the SGCA gene. This alteration results from a A to G substitution at nucleotide position 115, causing the threonine (T) at amino acid position 39 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(Feb 21, 2020)
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no assertion criteria provided
Method: clinical testing
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Limb-girdle muscular dystrophy type 2D
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002087548.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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. |
Citations for germline classification of this variant
HelpThere 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 rs540292629 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.