This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 801 of the FCHO1 protein (p.Val801Ile). This variant is present in population databases (rs139967668, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with FCHO1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1498544). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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_015122.3(FCHO1):c.2401G>A (p.Val801Ile)
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.
Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(1)
Uncertain significance(1); Likely benign(1)
2
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_015122.3(FCHO1):c.2401G>A (p.Val801Ile)
Variation ID: 1498544 Accession: VCV001498544.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.11 19: 17784899 (GRCh38) [ NCBI UCSC ] 19: 17895708 (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 Mar 28, 2022 Oct 8, 2024 Sep 20, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_015122.3:c.2401G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_055937.1:p.Val801Ile missense NM_001161357.2:c.2401G>A NP_001154829.1:p.Val801Ile missense NM_001161358.2:c.2401G>A NP_001154830.1:p.Val801Ile missense NM_001161359.2:c.2251G>A NP_001154831.1:p.Val751Ile missense NM_001384370.1:c.2401G>A NP_001371299.1:p.Val801Ile missense NM_001384371.1:c.2401G>A NP_001371300.1:p.Val801Ile missense NM_001384372.1:c.2401G>A NP_001371301.1:p.Val801Ile missense NM_001384373.1:c.2401G>A NP_001371302.1:p.Val801Ile missense NM_001384374.1:c.2401G>A NP_001371303.1:p.Val801Ile missense NM_001384375.1:c.2401G>A NP_001371304.1:p.Val801Ile missense NM_001384376.1:c.2401G>A NP_001371305.1:p.Val801Ile missense NM_001384377.1:c.2401G>A NP_001371306.1:p.Val801Ile missense NM_001384378.1:c.2401G>A NP_001371307.1:p.Val801Ile missense NM_001384379.1:c.2401G>A NP_001371308.1:p.Val801Ile missense NM_001384380.1:c.2401G>A NP_001371309.1:p.Val801Ile missense NM_001384381.1:c.2401G>A NP_001371310.1:p.Val801Ile missense NM_001384384.1:c.2251G>A NP_001371313.1:p.Val751Ile missense NM_001384385.1:c.2251G>A NP_001371314.1:p.Val751Ile missense NM_001384386.1:c.2251G>A NP_001371315.1:p.Val751Ile missense NM_001384387.1:c.2380G>A NP_001371316.1:p.Val794Ile missense NM_001384388.1:c.2362G>A NP_001371317.1:p.Val788Ile missense NM_001384389.1:c.2362G>A NP_001371318.1:p.Val788Ile missense NM_001384390.1:c.2326G>A NP_001371319.1:p.Val776Ile missense NM_001384391.1:c.2226+664G>A intron variant NM_001384392.1:c.2284G>A NP_001371321.1:p.Val762Ile missense NM_001384393.1:c.2284G>A NP_001371322.1:p.Val762Ile missense NM_001384394.1:c.2284G>A NP_001371323.1:p.Val762Ile missense NM_001384395.1:c.2284G>A NP_001371324.1:p.Val762Ile missense NM_001384396.1:c.2125G>A NP_001371325.1:p.Val709Ile missense NM_001384397.1:c.2125G>A NP_001371326.1:p.Val709Ile missense NM_001384398.1:c.2125G>A NP_001371327.1:p.Val709Ile missense NM_001384399.1:c.2125G>A NP_001371328.1:p.Val709Ile missense NM_001384400.1:c.2125G>A NP_001371329.1:p.Val709Ile missense NM_001384401.1:c.2125G>A NP_001371330.1:p.Val709Ile missense NM_001384402.1:c.2125G>A NP_001371331.1:p.Val709Ile missense NM_001384403.1:c.2080G>A NP_001371332.1:p.Val694Ile missense NM_001384404.1:c.1950+664G>A intron variant NM_001384405.1:c.2055-1675G>A intron variant NM_001384406.1:c.1800+664G>A intron variant NM_001384407.1:c.1524-1675G>A intron variant NR_169219.1:n.2658G>A non-coding transcript variant NR_169220.1:n.2472G>A non-coding transcript variant NR_169221.1:n.2413G>A non-coding transcript variant NR_169222.1:n.2581G>A non-coding transcript variant NR_169223.1:n.2384G>A non-coding transcript variant NR_169224.1:n.2294G>A non-coding transcript variant NR_169225.1:n.2861G>A non-coding transcript variant NR_169226.1:n.2564G>A non-coding transcript variant NR_169227.1:n.2655G>A non-coding transcript variant NR_169228.1:n.2493G>A non-coding transcript variant NR_169229.1:n.2854G>A non-coding transcript variant NR_169230.1:n.2391G>A non-coding transcript variant NR_169231.1:n.2540G>A non-coding transcript variant NR_169232.1:n.2931G>A non-coding transcript variant NR_169233.1:n.2468G>A non-coding transcript variant NR_169234.1:n.2934G>A non-coding transcript variant NR_169235.1:n.2281G>A non-coding transcript variant NR_169236.1:n.2857G>A non-coding transcript variant NR_169238.1:n.2567G>A non-coding transcript variant NR_169239.1:n.2840G>A non-coding transcript variant NR_169240.1:n.2487G>A non-coding transcript variant NR_169246.1:n.2382G>A non-coding transcript variant NR_169247.1:n.2563G>A non-coding transcript variant NR_169248.1:n.2654G>A non-coding transcript variant NR_169249.1:n.2341G>A non-coding transcript variant NR_169250.1:n.2282G>A non-coding transcript variant NR_169251.1:n.2763G>A non-coding transcript variant NR_169252.1:n.2617G>A non-coding transcript variant NR_169253.1:n.2312G>A non-coding transcript variant NR_169254.1:n.2792G>A non-coding transcript variant NR_169255.1:n.2316G>A non-coding transcript variant NR_169256.1:n.2688G>A non-coding transcript variant NR_169258.1:n.2432G>A non-coding transcript variant NR_169259.1:n.2614G>A non-coding transcript variant NR_169260.1:n.2887G>A non-coding transcript variant NC_000019.10:g.17784899G>A NC_000019.9:g.17895708G>A - Protein change
- V751I, V788I, V794I, V801I, V694I, V762I, V776I, V709I
- Other names
- -
- Canonical SPDI
- NC_000019.10:17784898:G:A
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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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0.00180 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00044
Trans-Omics for Precision Medicine (TOPMed) 0.00046
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00077
1000 Genomes Project 0.00180
1000 Genomes Project 30x 0.00187
- 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. |
|||
| FCHO1 | - | - |
GRCh38 GRCh37 |
643 | 671 | |
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
|
Aug 15, 2022 | RCV001999263.3 | |
| Likely benign (1) |
criteria provided, single submitter
|
Sep 20, 2024 | RCV004729025.1 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Aug 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002286012.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 801 of the FCHO1 protein (p.Val801Ile). … (more)
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 801 of the FCHO1 protein (p.Val801Ile). This variant is present in population databases (rs139967668, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with FCHO1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1498544). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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)
|
|
|
Likely benign
(Sep 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Immunodeficiency 76
Affected status: no
Allele origin:
germline
|
3billion
Accession: SCV005328735.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous … (more)
The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. (less)
|
Comment:
Comment:
The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.
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 sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 801 of the FCHO1 protein (p.Val801Ile). This variant is present in population databases (rs139967668, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with FCHO1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1498544). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.
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 rs139967668 ...
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.