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_003896.4(ST3GAL5):c.1247G>T (p.Arg416Leu)
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.
(9)
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
9
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_003896.4(ST3GAL5):c.1247G>T (p.Arg416Leu)
Variation ID: 198500 Accession: VCV000198500.23
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2p11.2 2: 85840154 (GRCh38) [ NCBI UCSC ] 2: 86067277 (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 5, 2015 May 1, 2024 Dec 14, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_003896.4:c.1247G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003887.3:p.Arg416Leu missense NM_001042437.2:c.1178G>T NP_001035902.1:p.Arg393Leu missense NM_001354223.2:c.863G>T NP_001341152.1:p.Arg288Leu missense NM_001354224.2:c.863G>T NP_001341153.1:p.Arg288Leu missense NM_001354226.2:c.863G>T NP_001341155.1:p.Arg288Leu missense NM_001354227.2:c.1163G>T NP_001341156.1:p.Arg388Leu missense NM_001354229.2:c.1163G>T NP_001341158.1:p.Arg388Leu missense NM_001354233.2:c.863G>T NP_001341162.1:p.Arg288Leu missense NM_001354234.1:c.863G>T NP_001341163.1:p.Arg288Leu missense NM_001354238.1:c.1163G>T NP_001341167.1:p.Arg388Leu missense NM_001354247.1:c.524G>T NP_001341176.1:p.Arg175Leu missense NM_001354248.1:c.863G>T NP_001341177.1:p.Arg288Leu missense NM_001363847.1:c.1088G>T NP_001350776.1:p.Arg363Leu missense NC_000002.12:g.85840154C>A NC_000002.11:g.86067277C>A NG_012807.1:g.53881G>T - Protein change
- R416L, R175L, R388L, R288L, R363L, R393L
- Other names
- -
- Canonical SPDI
- NC_000002.12:85840153: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.
-
The Genome Aggregation Database (gnomAD) 0.00028
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
Trans-Omics for Precision Medicine (TOPMed) 0.00038
- 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. |
|||
| ST3GAL5 | - | - |
GRCh38 GRCh37 |
381 | 477 | |
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 (4) |
criteria provided, multiple submitters, no conflicts
|
Oct 24, 2022 | RCV000352472.15 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 6, 2014 | RCV000194785.8 | |
| Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 29, 2019 | RCV000713526.10 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Dec 14, 2022 | RCV002516803.2 |
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
(Nov 06, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000249056.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
|
|
|
Uncertain significance
(Feb 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000232180.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Uncertain significance
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
GM3 synthase deficiency
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000432353.3
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
(Mar 14, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000844148.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
|
|
|
Uncertain significance
(Mar 04, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
GM3 synthase deficiency
Affected status: yes
Allele origin:
paternal
|
Baylor Genetics
Accession: SCV001520494.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
|
|
|
Uncertain significance
(May 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
GM3 synthase deficiency
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002796903.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Uncertain significance
(Oct 24, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
GM3 synthase deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000835061.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 416 of the ST3GAL5 protein (p.Arg416Leu). … (more)
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 416 of the ST3GAL5 protein (p.Arg416Leu). This variant is present in population databases (rs200683924, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 198500). 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)
|
|
|
Uncertain significance
(Jul 29, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001991661.2
First in ClinVar: Nov 06, 2021 Last updated: Mar 04, 2023 |
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
(Dec 14, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003686297.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.1247G>T (p.R416L) alteration is located in exon 7 (coding exon 7) of the ST3GAL5 gene. This alteration results from a G to T substitution … (more)
The c.1247G>T (p.R416L) alteration is located in exon 7 (coding exon 7) of the ST3GAL5 gene. This alteration results from a G to T substitution at nucleotide position 1247, causing the arginine (R) at amino acid position 416 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 416 of the ST3GAL5 protein (p.Arg416Leu). This variant is present in population databases (rs200683924, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 198500). 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.
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:
The c.1247G>T (p.R416L) alteration is located in exon 7 (coding exon 7) of the ST3GAL5 gene. This alteration results from a G to T substitution at nucleotide position 1247, causing the arginine (R) at amino acid position 416 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
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:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 416 of the ST3GAL5 protein (p.Arg416Leu). This variant is present in population databases (rs200683924, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with ST3GAL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 198500). 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.
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:
The c.1247G>T (p.R416L) alteration is located in exon 7 (coding exon 7) of the ST3GAL5 gene. This alteration results from a G to T substitution at nucleotide position 1247, causing the arginine (R) at amino acid position 416 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ST3GAL5 | - | - | - | - |
Text-mined citations for rs200683924 ...
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 Sep 29, 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.