ClinVar contains an entry for this variant (Variation ID: 2075443). This variant has not been reported in the literature in individuals affected with CAST-related conditions. This variant is present in population databases (rs201451322, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 592 of the CAST protein (p.Thr592Met). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
ClinVar Genomic variation as it relates to human health
NM_001750.7(CAST):c.1898C>T (p.Thr633Met)
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.
(1)
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
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001750.7(CAST):c.1898C>T (p.Thr633Met)
Variation ID: 2075443 Accession: VCV002075443.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q15 5: 96762338 (GRCh38) [ NCBI UCSC ] 5: 96098042 (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 8, 2023 Feb 14, 2024 Aug 10, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001750.7:c.1898C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001741.4:p.Thr633Met missense NM_001042440.5:c.1775C>T NP_001035905.1:p.Thr592Met missense NM_001042441.3:c.1841C>T NP_001035906.1:p.Thr614Met missense NM_001042442.3:c.1832C>T NP_001035907.1:p.Thr611Met missense NM_001042443.3:c.1649C>T NP_001035908.1:p.Thr550Met missense NM_001042444.3:c.1526C>T NP_001035909.1:p.Thr509Met missense NM_001042445.3:c.1544C>T NP_001035910.1:p.Thr515Met missense NM_001042446.3:c.1487C>T NP_001035911.1:p.Thr496Met missense NM_001190442.2:c.1610C>T NP_001177371.1:p.Thr537Met missense NM_001284212.4:c.1526C>T NP_001271141.1:p.Thr509Met missense NM_001284213.4:c.1433C>T NP_001271142.1:p.Thr478Met missense NM_001330626.2:c.1802C>T NP_001317555.1:p.Thr601Met missense NM_001330627.2:c.1775C>T NP_001317556.1:p.Thr592Met missense NM_001330628.2:c.1730C>T NP_001317557.1:p.Thr577Met missense NM_001330629.2:c.1814C>T NP_001317558.1:p.Thr605Met missense NM_001330630.2:c.1487C>T NP_001317559.1:p.Thr496Met missense NM_001330631.2:c.1610C>T NP_001317560.1:p.Thr537Met missense NM_001330632.2:c.1583C>T NP_001317561.1:p.Thr528Met missense NM_001330633.2:c.1592C>T NP_001317562.1:p.Thr531Met missense NM_001330634.2:c.1553C>T NP_001317563.1:p.Thr518Met missense NM_001349244.2:c.*862G>A 3 prime UTR NM_001375317.1:c.1787C>T NP_001362246.1:p.Thr596Met missense NM_001423250.1:c.1649C>T NP_001410179.1:p.Thr550Met missense NM_001423251.1:c.1610C>T NP_001410180.1:p.Thr537Met missense NM_001423252.1:c.1610C>T NP_001410181.1:p.Thr537Met missense NM_001423253.1:c.1583C>T NP_001410182.1:p.Thr528Met missense NM_001423254.1:c.1583C>T NP_001410183.1:p.Thr528Met missense NM_001423255.1:c.1544C>T NP_001410184.1:p.Thr515Met missense NM_001423256.1:c.1544C>T NP_001410185.1:p.Thr515Met missense NM_001423257.1:c.1544C>T NP_001410186.1:p.Thr515Met missense NM_001423258.1:c.1544C>T NP_001410187.1:p.Thr515Met missense NM_001423259.1:c.1544C>T NP_001410188.1:p.Thr515Met missense NM_001423260.1:c.1487C>T NP_001410189.1:p.Thr496Met missense NM_016442.5:c.*862G>A 3 prime UTR NM_173060.5:c.1583C>T NP_775083.1:p.Thr528Met missense NR_104285.2:n.843C>T non-coding transcript variant NC_000005.10:g.96762338C>T NC_000005.9:g.96098042C>T NG_027839.2:g.178646G>A NG_029490.2:g.105302C>T - Protein change
- T496M, T509M, T518M, T537M, T601M, T614M, T633M, T531M, T550M, T577M, T592M, T596M, T478M, T515M, T528M, T605M, T611M
- Other names
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- Canonical SPDI
- NC_000005.10:96762337:C:T
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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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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- 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. |
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| CAST | - | - |
GRCh38 GRCh37 |
146 | 641 | |
| ERAP1 | - | - |
GRCh38 GRCh37 |
111 | 268 | |
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 (1) |
criteria provided, single submitter
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Aug 10, 2023 | RCV002982479.10 |
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. |
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Uncertain significance
(Aug 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003289590.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 2075443). This variant has not been reported in the literature in individuals affected with CAST-related conditions. … (more)
ClinVar contains an entry for this variant (Variation ID: 2075443). This variant has not been reported in the literature in individuals affected with CAST-related conditions. This variant is present in population databases (rs201451322, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 592 of the CAST protein (p.Thr592Met). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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)
|
Comment:
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:
ClinVar contains an entry for this variant (Variation ID: 2075443). This variant has not been reported in the literature in individuals affected with CAST-related conditions. This variant is present in population databases (rs201451322, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 592 of the CAST protein (p.Thr592Met). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
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 this variant ...
HelpRecord last updated Nov 10, 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.