This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ClinVar Genomic variation as it relates to human health
NM_025243.4(SLC19A3):c.977G>T (p.Gly326Val)
Germline
Classification
Help
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.
(7)
Help
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
7
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_025243.4(SLC19A3):c.977G>T (p.Gly326Val)
Variation ID: 334879 Accession: VCV000334879.15
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q36.3 2: 227698738 (GRCh38) [ NCBI UCSC ] 2: 228563454 (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 6, 2016 May 1, 2024 Oct 13, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_025243.4:c.977G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_079519.1:p.Gly326Val missense NC_000002.12:g.227698738C>A NC_000002.11:g.228563454C>A NG_016359.1:g.24292G>T - Protein change
- G326V
- Other names
- -
- Canonical SPDI
- NC_000002.12:227698737:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00006
The Genome Aggregation Database (gnomAD) 0.00016
Trans-Omics for Precision Medicine (TOPMed) 0.00022
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| SLC19A3 | - | - |
GRCh38 GRCh37 |
670 | 695 | |
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. |
|---|---|---|---|---|
| Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
|
Oct 13, 2022 | RCV000684964.15 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
May 17, 2019 | RCV001556309.2 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 12, 2021 | RCV002521413.2 |
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
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Biotin-responsive basal ganglia disease
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000895401.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
|
Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Biotin-responsive basal ganglia disease
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000428295.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
|
|
|
Uncertain significance
(May 17, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001777868.1
First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021 |
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as … (more)
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
|
|
|
Uncertain significance
(Oct 13, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Biotin-responsive basal ganglia disease
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000812429.5
First in ClinVar: Oct 10, 2018 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 326 of the SLC19A3 protein (p.Gly326Val). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 326 of the SLC19A3 protein (p.Gly326Val). This variant is present in population databases (rs747823282, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC19A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 334879). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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)
|
|
|
Uncertain significance
(Jan 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Biotin-responsive basal ganglia disease
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV003836102.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
|
|
|
Uncertain significance
(Nov 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003660182.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.977G>T (p.G326V) alteration is located in exon 3 (coding exon 2) of the SLC19A3 gene. This alteration results from a G to T substitution … (more)
The c.977G>T (p.G326V) alteration is located in exon 3 (coding exon 2) of the SLC19A3 gene. This alteration results from a G to T substitution at nucleotide position 977, causing the glycine (G) at amino acid position 326 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Biotin-responsive basal ganglia disease
Affected status: unknown
Allele origin:
unknown
|
GenomeConnect - Brain Gene Registry
Accession: SCV004012838.1
First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023 |
Comment:
Variant interpreted as Uncertain significance and reported on 03-25-2018 by Lab Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. … (more)
Variant interpreted as Uncertain significance and reported on 03-25-2018 by Lab Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less)
Clinical Features:
Phenotypic abnormality (present)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: male
Method: Gene Panel Sequencing
Testing laboratory: Invitae
Date variant was reported to submitter: 2018-03-25
Testing laboratory interpretation: Uncertain significance
|
Comment:
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 326 of the SLC19A3 protein (p.Gly326Val). This variant is present in population databases (rs747823282, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC19A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 334879). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Comment:
The c.977G>T (p.G326V) alteration is located in exon 3 (coding exon 2) of the SLC19A3 gene. This alteration results from a G to T substitution at nucleotide position 977, causing the glycine (G) at amino acid position 326 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Comment:
Variant interpreted as Uncertain significance and reported on 03-25-2018 by Lab Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.
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:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Comment:
In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 326 of the SLC19A3 protein (p.Gly326Val). This variant is present in population databases (rs747823282, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC19A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 334879). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Comment:
The c.977G>T (p.G326V) alteration is located in exon 3 (coding exon 2) of the SLC19A3 gene. This alteration results from a G to T substitution at nucleotide position 977, causing the glycine (G) at amino acid position 326 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Comment:
Variant interpreted as Uncertain significance and reported on 03-25-2018 by Lab Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.
Citations for germline classification of this variant
Help| There 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 rs747823282 ...
HelpThese 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 08, 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.