This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 49 of the RBFOX3 protein (p.Thr49Ala). This variant has not been reported in the literature in individuals affected with RBFOX3-related conditions. 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0").
ClinVar Genomic variation as it relates to human health
NM_001350451.2(RBFOX3):c.145A>G (p.Thr49Ala)
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.
(2)
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
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001350451.2(RBFOX3):c.145A>G (p.Thr49Ala)
Variation ID: 1976877 Accession: VCV001976877.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q25.3 17: 79115571 (GRCh38) [ NCBI UCSC ] 17: 77111653 (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 7, 2023 May 1, 2024 Nov 1, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001350451.2:c.145A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001337380.1:p.Thr49Ala missense NM_001082575.3:c.145A>G NP_001076044.1:p.Thr49Ala missense NM_001350453.2:c.145A>G NP_001337382.1:p.Thr49Ala missense NM_001385804.1:c.145A>G NP_001372733.1:p.Thr49Ala missense NM_001385805.1:c.145A>G NP_001372734.1:p.Thr49Ala missense NM_001385806.1:c.145A>G NP_001372735.1:p.Thr49Ala missense NM_001385807.1:c.145A>G NP_001372736.1:p.Thr49Ala missense NM_001385808.1:c.145A>G NP_001372737.1:p.Thr49Ala missense NM_001385809.1:c.145A>G NP_001372738.1:p.Thr49Ala missense NM_001385810.1:c.145A>G NP_001372739.1:p.Thr49Ala missense NM_001385811.1:c.145A>G NP_001372740.1:p.Thr49Ala missense NM_001385812.1:c.145A>G NP_001372741.1:p.Thr49Ala missense NM_001385813.1:c.145A>G NP_001372742.1:p.Thr49Ala missense NM_001385814.1:c.145A>G NP_001372743.1:p.Thr49Ala missense NM_001385815.1:c.145A>G NP_001372744.1:p.Thr49Ala missense NM_001385816.1:c.145A>G NP_001372745.1:p.Thr49Ala missense NM_001385817.1:c.145A>G NP_001372746.1:p.Thr49Ala missense NM_001385818.1:c.145A>G NP_001372747.1:p.Thr49Ala missense NM_001385819.1:c.145A>G NP_001372748.1:p.Thr49Ala missense NM_001385820.1:c.145A>G NP_001372749.1:p.Thr49Ala missense NM_001385821.1:c.145A>G NP_001372750.1:p.Thr49Ala missense NM_001385822.1:c.145A>G NP_001372751.1:p.Thr49Ala missense NM_001385823.1:c.145A>G NP_001372752.1:p.Thr49Ala missense NM_001385824.1:c.145A>G NP_001372753.1:p.Thr49Ala missense NM_001385825.1:c.145A>G NP_001372754.1:p.Thr49Ala missense NM_001385826.1:c.145A>G NP_001372755.1:p.Thr49Ala missense NM_001385827.1:c.145A>G NP_001372756.1:p.Thr49Ala missense NM_001385828.1:c.145A>G NP_001372757.1:p.Thr49Ala missense NM_001385829.1:c.145A>G NP_001372758.1:p.Thr49Ala missense NM_001385830.1:c.145A>G NP_001372759.1:p.Thr49Ala missense NM_001385831.1:c.145A>G NP_001372760.1:p.Thr49Ala missense NM_001385832.1:c.145A>G NP_001372761.1:p.Thr49Ala missense NM_001385833.1:c.145A>G NP_001372762.1:p.Thr49Ala missense NM_001385834.1:c.145A>G NP_001372763.1:p.Thr49Ala missense NM_001385835.1:c.145A>G NP_001372764.1:p.Thr49Ala missense NM_001385836.1:c.145A>G NP_001372765.1:p.Thr49Ala missense NM_001385837.1:c.145A>G NP_001372766.1:p.Thr49Ala missense NM_001385838.1:c.145A>G NP_001372767.1:p.Thr49Ala missense NM_001385839.1:c.145A>G NP_001372768.1:p.Thr49Ala missense NM_001385840.1:c.145A>G NP_001372769.1:p.Thr49Ala missense NM_001385841.1:c.145A>G NP_001372770.1:p.Thr49Ala missense NM_001385842.1:c.145A>G NP_001372771.1:p.Thr49Ala missense NM_001385843.1:c.145A>G NP_001372772.1:p.Thr49Ala missense NM_001385844.1:c.145A>G NP_001372773.1:p.Thr49Ala missense NM_001385845.1:c.145A>G NP_001372774.1:p.Thr49Ala missense NM_001385846.1:c.145A>G NP_001372775.1:p.Thr49Ala missense NM_001385847.1:c.145A>G NP_001372776.1:p.Thr49Ala missense NC_000017.11:g.79115571T>C NC_000017.10:g.77111653T>C NG_053112.1:g.500633A>G NG_053112.2:g.555000A>G - Protein change
- T49A
- Other names
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- Canonical SPDI
- NC_000017.11:79115570:T:C
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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. |
|||
| RBFOX3 | - | - |
GRCh38 GRCh37 |
294 | 322 | |
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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May 20, 2022 | RCV002736348.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Nov 1, 2022 | RCV004067875.1 |
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
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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|---|---|---|---|---|---|
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Uncertain significance
(May 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Idiopathic generalized epilepsy
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003010786.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is … (more)
This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 49 of the RBFOX3 protein (p.Thr49Ala). This variant has not been reported in the literature in individuals affected with RBFOX3-related conditions. 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). (less)
|
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Uncertain significance
(Nov 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003658519.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.145A>G (p.T49A) alteration is located in exon 4 (coding exon 1) of the RBFOX3 gene. This alteration results from a A to G substitution … (more)
The c.145A>G (p.T49A) alteration is located in exon 4 (coding exon 1) of the RBFOX3 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the threonine (T) at amino acid position 49 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The c.145A>G (p.T49A) alteration is located in exon 4 (coding exon 1) of the RBFOX3 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the threonine (T) at amino acid position 49 to be replaced by an alanine (A). 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 is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 49 of the RBFOX3 protein (p.Thr49Ala). This variant has not been reported in the literature in individuals affected with RBFOX3-related conditions. 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0").
Comment:
The c.145A>G (p.T49A) alteration is located in exon 4 (coding exon 1) of the RBFOX3 gene. This alteration results from a A to G substitution at nucleotide position 145, causing the threonine (T) at amino acid position 49 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
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 25, 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.