ClinVar Genomic variation as it relates to human health
NM_001385875.1(ZFYVE27):c.572G>T (p.Gly191Val)
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.
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); Benign(4); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001385875.1(ZFYVE27):c.572G>T (p.Gly191Val)
Variation ID: 1289 Accession: VCV000001289.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q24.2 10: 97749494 (GRCh38) [ NCBI UCSC ] 10: 99509251 (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 Jul 15, 2016 Feb 28, 2024 Jan 18, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001385875.1:c.572G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001372804.1:p.Gly191Val missense NM_001002261.4:c.572G>T NP_001002261.1:p.Gly191Val missense NM_001002262.4:c.572G>T NP_001002262.1:p.Gly191Val missense NM_001174119.2:c.476G>T NP_001167590.1:p.Gly159Val missense NM_001174120.2:c.314G>T NP_001167591.1:p.Gly105Val missense NM_001174121.2:c.278G>T NP_001167592.1:p.Gly93Val missense NM_001174122.2:c.218G>T NP_001167593.1:p.Gly73Val missense NM_001385871.1:c.572G>T NP_001372800.1:p.Gly191Val missense NM_001385876.1:c.611G>T NP_001372805.1:p.Gly204Val missense NM_001385877.1:c.572G>T NP_001372806.1:p.Gly191Val missense NM_001385878.1:c.572G>T NP_001372807.1:p.Gly191Val missense NM_001385879.1:c.572G>T NP_001372808.1:p.Gly191Val missense NM_001385880.1:c.572G>T NP_001372809.1:p.Gly191Val missense NM_001385881.1:c.536G>T NP_001372810.1:p.Gly179Val missense NM_001385882.1:c.572G>T NP_001372811.1:p.Gly191Val missense NM_001385883.1:c.572G>T NP_001372812.1:p.Gly191Val missense NM_001385884.1:c.572G>T NP_001372813.1:p.Gly191Val missense NM_001385885.1:c.476G>T NP_001372814.1:p.Gly159Val missense NM_001385886.1:c.476G>T NP_001372815.1:p.Gly159Val missense NM_001385887.1:c.476G>T NP_001372816.1:p.Gly159Val missense NM_001385888.1:c.476G>T NP_001372817.1:p.Gly159Val missense NM_001385889.1:c.476G>T NP_001372818.1:p.Gly159Val missense NM_001385890.1:c.368G>T NP_001372819.1:p.Gly123Val missense NM_001385891.1:c.368G>T NP_001372820.1:p.Gly123Val missense NM_001385892.1:c.368G>T NP_001372821.1:p.Gly123Val missense NM_001385893.1:c.368G>T NP_001372822.1:p.Gly123Val missense NM_001385894.1:c.368G>T NP_001372823.1:p.Gly123Val missense NM_001385895.1:c.368G>T NP_001372824.1:p.Gly123Val missense NM_001385896.1:c.368G>T NP_001372825.1:p.Gly123Val missense NM_001385897.1:c.368G>T NP_001372826.1:p.Gly123Val missense NM_001385898.1:c.368G>T NP_001372827.1:p.Gly123Val missense NM_001385899.1:c.335G>T NP_001372828.1:p.Gly112Val missense NM_001385900.1:c.335G>T NP_001372829.1:p.Gly112Val missense NM_001385901.1:c.314G>T NP_001372830.1:p.Gly105Val missense NM_001385902.1:c.314G>T NP_001372831.1:p.Gly105Val missense NM_001385903.1:c.335G>T NP_001372832.1:p.Gly112Val missense NM_001385904.1:c.335G>T NP_001372833.1:p.Gly112Val missense NM_001385905.1:c.335G>T NP_001372834.1:p.Gly112Val missense NM_001385906.1:c.314G>T NP_001372835.1:p.Gly105Val missense NM_001385908.1:c.314G>T NP_001372837.1:p.Gly105Val missense NM_001385911.1:c.314G>T NP_001372840.1:p.Gly105Val missense NM_001385915.1:c.278G>T NP_001372844.1:p.Gly93Val missense NM_001385916.1:c.239G>T NP_001372845.1:p.Gly80Val missense NM_001385918.1:c.218G>T NP_001372847.1:p.Gly73Val missense NM_001385919.1:c.32-837G>T intron variant NM_144588.7:c.572G>T NP_653189.3:p.Gly191Val missense NR_169794.1:n.742G>T non-coding transcript variant NR_169795.1:n.700G>T non-coding transcript variant NR_169796.1:n.767G>T non-coding transcript variant NR_169798.1:n.731G>T non-coding transcript variant NR_169799.1:n.388G>T non-coding transcript variant NR_169801.1:n.767G>T non-coding transcript variant NR_169802.1:n.413G>T non-coding transcript variant NR_169803.1:n.742G>T non-coding transcript variant NR_169804.1:n.760G>T non-coding transcript variant NR_169805.1:n.771G>T non-coding transcript variant NR_169806.1:n.756G>T non-coding transcript variant NR_169808.1:n.799G>T non-coding transcript variant NR_169809.1:n.696G>T non-coding transcript variant NR_169810.1:n.767G>T non-coding transcript variant NR_169811.1:n.731G>T non-coding transcript variant NC_000010.11:g.97749494G>T NC_000010.10:g.99509251G>T NG_017075.1:g.17374G>T Q5T4F4:p.Gly191Val - Protein change
- G191V, G159V, G105V, G73V, G93V, G112V, G123V, G179V, G204V, G80V
- Other names
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- Canonical SPDI
- NC_000010.11:97749493:G: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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0.02616 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00987
Exome Aggregation Consortium (ExAC) 0.01095
1000 Genomes Project 0.02616
The Genome Aggregation Database (gnomAD) 0.02717
1000 Genomes Project 30x 0.02764
Trans-Omics for Precision Medicine (TOPMed) 0.02859
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 | ||
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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 |
187 | 210 |
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. |
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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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May 28, 2019 | RCV000001352.15 | |
Benign (3) |
criteria provided, single submitter
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Jun 25, 2015 | RCV000407569.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 28, 2013 | RCV000415084.2 | |
Benign (1) |
criteria provided, single submitter
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Jan 18, 2024 | RCV000471962.9 | |
Benign (1) |
criteria provided, single submitter
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Jan 4, 2021 | RCV001723530.2 |
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. |
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Uncertain significance
(Nov 28, 2013)
|
criteria provided, single submitter
Method: clinical testing
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Spastic tetraparesis
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000493051.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 33
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000366369.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
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Uncertain significance
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 33
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001369545.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Uncertain significance.
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Benign
(Jan 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001950694.2
First in ClinVar: Oct 02, 2021 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 18606302, 20981092, 16826525, 27884173)
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Benign
(Jan 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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Spastic paraplegia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000556810.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Benign
(Jun 25, 2015)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000332544.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 33
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138156.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Pathogenic
(May 09, 2014)
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no assertion criteria provided
Method: literature only
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SPASTIC PARAPLEGIA 33, AUTOSOMAL DOMINANT
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000021502.5
First in ClinVar: Apr 04, 2013 Last updated: Jul 15, 2016 |
Comment on evidence:
In affected members of a 5-generation German family with hereditary spastic paraplegia (SPG33; 610244), Mannan et al. (2006) found a G-to-T transversion at position 572 … (more)
In affected members of a 5-generation German family with hereditary spastic paraplegia (SPG33; 610244), Mannan et al. (2006) found a G-to-T transversion at position 572 in exon 6 of the ZFYVE27 cDNA. The mutation produced a gly191-to-val (G191V) substitution. The G191V mutation (G105V in isoform c of the protein) is located near the third transmembrane motif and shifts the transmembrane motif forward by 3 amino acids. Mannan et al. (2006) observed that expression of the mutated protein showed an aberrant intracellular pattern in tubular structures and that its interaction with spastin was severely affected. Martignoni et al. (2008) commented that they found no difference in the ability of wildtype or G191V-mutant protrudin to extend neurites in cellular functional expression studies. The G191V-mutant protein was also found to interact with Rab11-GDP (605570) and spastin (604277), indicating that the mutation did not lead to loss of function. Martignoni et al. (2008) stated that G191V (rs35077384) had been identified as a SNP in several populations, with an allele frequency ranging from 0.008 to 0.067, thus casting doubt on the pathogenicity of this mutation. Mannan (2008) replied that their studies showed a decreased interaction between G191V-mutant protrudin and spastin and explained that discrepancies could be due to the different assays used or the variable effect of G191V-mutant protrudin in different ethnic populations. Hashimoto et al. (2014) found that expression of G191V-mutant human protrudin mildly enhanced the sensitivity of mouse Neuro2a neuroblasts to several cell stressors. G191V-mutant protrudin had a markedly longer half-life and was detected in larger protein complexes than wildtype protrudin. (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001930785.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001963288.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Protrudin regulates endoplasmic reticulum morphology and function associated with the pathogenesis of hereditary spastic paraplegia. | Hashimoto Y | The Journal of biological chemistry | 2014 | PMID: 24668814 |
The role of ZFYVE27/protrudin in hereditary spastic paraplegia. | Martignoni M | American journal of human genetics | 2008 | PMID: 18606302 |
ZFYVE27 (SPG33), a novel spastin-binding protein, is mutated in hereditary spastic paraplegia. | Mannan AU | American journal of human genetics | 2006 | PMID: 16826525 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ZFYVE27 | - | - | - | - |
Text-mined citations for rs35077384 ...
HelpRecord last updated Mar 05, 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.