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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with ZFYVE27-related conditions. This variant is present in population databases (rs367545791, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 97 of the ZFYVE27 protein (p.Ala97Val).
ClinVar Genomic variation as it relates to human health
NM_001385875.1(ZFYVE27):c.290C>T (p.Ala97Val)
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_001385875.1(ZFYVE27):c.290C>T (p.Ala97Val)
Variation ID: 1990783 Accession: VCV001990783.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q24.2 10: 97744750 (GRCh38) [ NCBI UCSC ] 10: 99504507 (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 May 1, 2024 Nov 5, 2022 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001385875.1:c.290C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001372804.1:p.Ala97Val missense NM_001002261.4:c.290C>T NP_001002261.1:p.Ala97Val missense NM_001002262.4:c.290C>T NP_001002262.1:p.Ala97Val missense NM_001174119.2:c.194C>T NP_001167590.1:p.Ala65Val missense NM_001174120.2:c.198-3519C>T intron variant NM_001174121.2:c.-5C>T 5 prime UTR NM_001174122.2:c.198-4724C>T intron variant NM_001385871.1:c.290C>T NP_001372800.1:p.Ala97Val missense NM_001385876.1:c.329C>T NP_001372805.1:p.Ala110Val missense NM_001385877.1:c.290C>T NP_001372806.1:p.Ala97Val missense NM_001385878.1:c.290C>T NP_001372807.1:p.Ala97Val missense NM_001385879.1:c.290C>T NP_001372808.1:p.Ala97Val missense NM_001385880.1:c.290C>T NP_001372809.1:p.Ala97Val missense NM_001385881.1:c.269-15C>T intron variant NM_001385882.1:c.290C>T NP_001372811.1:p.Ala97Val missense NM_001385883.1:c.290C>T NP_001372812.1:p.Ala97Val missense NM_001385884.1:c.290C>T NP_001372813.1:p.Ala97Val missense NM_001385885.1:c.194C>T NP_001372814.1:p.Ala65Val missense NM_001385886.1:c.290C>T NP_001372815.1:p.Ala97Val missense NM_001385887.1:c.194C>T NP_001372816.1:p.Ala65Val missense NM_001385888.1:c.194C>T NP_001372817.1:p.Ala65Val missense NM_001385889.1:c.290C>T NP_001372818.1:p.Ala97Val missense NM_001385890.1:c.86C>T NP_001372819.1:p.Ala29Val missense NM_001385891.1:c.86C>T NP_001372820.1:p.Ala29Val missense NM_001385892.1:c.86C>T NP_001372821.1:p.Ala29Val missense NM_001385893.1:c.86C>T NP_001372822.1:p.Ala29Val missense NM_001385894.1:c.86C>T NP_001372823.1:p.Ala29Val missense NM_001385895.1:c.86C>T NP_001372824.1:p.Ala29Val missense NM_001385896.1:c.86C>T NP_001372825.1:p.Ala29Val missense NM_001385897.1:c.86C>T NP_001372826.1:p.Ala29Val missense NM_001385898.1:c.86C>T NP_001372827.1:p.Ala29Val missense NM_001385899.1:c.53C>T NP_001372828.1:p.Ala18Val missense NM_001385900.1:c.53C>T NP_001372829.1:p.Ala18Val missense NM_001385901.1:c.198-3519C>T intron variant NM_001385902.1:c.198-3519C>T intron variant NM_001385903.1:c.53C>T NP_001372832.1:p.Ala18Val missense NM_001385904.1:c.53C>T NP_001372833.1:p.Ala18Val missense NM_001385905.1:c.53C>T NP_001372834.1:p.Ala18Val missense NM_001385906.1:c.198-3519C>T intron variant NM_001385908.1:c.198-3519C>T intron variant NM_001385911.1:c.198-3519C>T intron variant NM_001385915.1:c.-5C>T 5 prime UTR NM_001385916.1:c.53C>T NP_001372845.1:p.Ala18Val missense NM_001385917.1:c.53C>T NP_001372846.1:p.Ala18Val missense NM_001385918.1:c.198-4724C>T intron variant NM_001385919.1:c.32-5581C>T intron variant NM_144588.7:c.290C>T NP_653189.3:p.Ala97Val missense NR_169794.1:n.460C>T non-coding transcript variant NR_169795.1:n.418C>T non-coding transcript variant NR_169796.1:n.485C>T non-coding transcript variant NR_169797.1:n.460C>T non-coding transcript variant NR_169798.1:n.460C>T non-coding transcript variant NR_169800.1:n.485C>T non-coding transcript variant NR_169801.1:n.485C>T non-coding transcript variant NR_169803.1:n.460C>T non-coding transcript variant NR_169804.1:n.489C>T non-coding transcript variant NR_169805.1:n.489C>T non-coding transcript variant NR_169806.1:n.485C>T non-coding transcript variant NR_169808.1:n.528C>T non-coding transcript variant NR_169809.1:n.414C>T non-coding transcript variant NR_169810.1:n.485C>T non-coding transcript variant NR_169811.1:n.460C>T non-coding transcript variant NC_000010.11:g.97744750C>T NC_000010.10:g.99504507C>T NG_017075.1:g.12630C>T - Protein change
- A110V, A29V, A18V, A97V, A65V
- Other names
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- Canonical SPDI
- NC_000010.11:97744749: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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| ZFYVE27 | - | - |
GRCh38 GRCh37 |
189 | 212 | |
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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Nov 5, 2022 | RCV002805838.3 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Aug 17, 2022 | RCV004064819.1 |
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
(Nov 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Spastic paraplegia
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003030248.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
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 … (more)
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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with ZFYVE27-related conditions. This variant is present in population databases (rs367545791, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 97 of the ZFYVE27 protein (p.Ala97Val). (less)
|
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Uncertain significance
(Aug 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003555604.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.290C>T (p.A97V) alteration is located in exon 3 (coding exon 3) of the ZFYVE27 gene. This alteration results from a C to T substitution … (more)
The c.290C>T (p.A97V) alteration is located in exon 3 (coding exon 3) of the ZFYVE27 gene. This alteration results from a C to T substitution at nucleotide position 290, causing the alanine (A) at amino acid position 97 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The c.290C>T (p.A97V) alteration is located in exon 3 (coding exon 3) of the ZFYVE27 gene. This alteration results from a C to T substitution at nucleotide position 290, causing the alanine (A) at amino acid position 97 to be replaced by a valine (V). 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:
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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with ZFYVE27-related conditions. This variant is present in population databases (rs367545791, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 97 of the ZFYVE27 protein (p.Ala97Val).
Comment:
The c.290C>T (p.A97V) alteration is located in exon 3 (coding exon 3) of the ZFYVE27 gene. This alteration results from a C to T substitution at nucleotide position 290, causing the alanine (A) at amino acid position 97 to be replaced by a valine (V). 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 Oct 27, 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.