ClinVar Genomic variation as it relates to human health
NM_012470.4(TNPO3):c.2326A>G (p.Ile776Val)
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(3); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_012470.4(TNPO3):c.2326A>G (p.Ile776Val)
Variation ID: 194964 Accession: VCV000194964.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q32.1 7: 128972530 (GRCh38) [ NCBI UCSC ] 7: 128612584 (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 Dec 6, 2016 May 1, 2024 Jan 15, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_012470.4:c.2326A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_036602.1:p.Ile776Val missense NM_001191028.3:c.2134A>G NP_001177957.2:p.Ile712Val missense NM_001382216.1:c.2428A>G NP_001369145.1:p.Ile810Val missense NM_001382217.1:c.2407A>G NP_001369146.1:p.Ile803Val missense NM_001382218.1:c.2326A>G NP_001369147.1:p.Ile776Val missense NM_001382219.1:c.2218A>G NP_001369148.1:p.Ile740Val missense NM_001382220.1:c.2185A>G NP_001369149.1:p.Ile729Val missense NM_001382221.1:c.2182A>G NP_001369150.1:p.Ile728Val missense NM_001382222.1:c.2179A>G NP_001369151.1:p.Ile727Val missense NM_001382223.1:c.2134A>G NP_001369152.1:p.Ile712Val missense NR_034053.3:n.2828A>G non-coding transcript variant NR_167911.1:n.2915A>G non-coding transcript variant NR_167912.1:n.2773A>G non-coding transcript variant NR_167913.1:n.2575A>G non-coding transcript variant NR_167914.1:n.2735A>G non-coding transcript variant NR_167915.1:n.2991A>G non-coding transcript variant NR_167916.1:n.2465A>G non-coding transcript variant NR_167917.1:n.2498A>G non-coding transcript variant NR_167918.1:n.2953A>G non-coding transcript variant NR_167919.1:n.2792A>G non-coding transcript variant NR_167920.1:n.2751A>G non-coding transcript variant NR_167921.1:n.2953A>G non-coding transcript variant NR_167922.1:n.2789A>G non-coding transcript variant NR_167923.1:n.2590A>G non-coding transcript variant NR_167924.1:n.2667A>G non-coding transcript variant NR_167925.1:n.2590A>G non-coding transcript variant NR_167926.1:n.2601A>G non-coding transcript variant NR_167927.1:n.2894A>G non-coding transcript variant NC_000007.14:g.128972530T>C NC_000007.13:g.128612584T>C NG_023428.1:g.87644A>G - Protein change
- I776V, I712V, I727V, I728V, I729V, I740V, I803V, I810V
- Other names
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- Canonical SPDI
- NC_000007.14:128972529: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.
The Genome Aggregation Database (gnomAD) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Exome Aggregation Consortium (ExAC) 0.00012
Trans-Omics for Precision Medicine (TOPMed) 0.00012
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
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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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TNPO3 | - | - |
GRCh38 GRCh37 |
608 | 665 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Jun 2, 2016 | RCV000175457.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 16, 2021 | RCV002516677.2 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 15, 2024 | RCV000531231.13 |
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
(Jun 02, 2016)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000226939.5
First in ClinVar: Jun 29, 2015 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 3
Sex: mixed
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Uncertain significance
(Apr 05, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant limb-girdle muscular dystrophy type 1F
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Accession: SCV001530702.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Likely benign
(Jan 15, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant limb-girdle muscular dystrophy type 1F
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000639521.9
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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Uncertain significance
(Sep 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003740801.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.2326A>G (p.I776V) alteration is located in exon 19 (coding exon 19) of the TNPO3 gene. This alteration results from a A to G substitution … (more)
The c.2326A>G (p.I776V) alteration is located in exon 19 (coding exon 19) of the TNPO3 gene. This alteration results from a A to G substitution at nucleotide position 2326, causing the isoleucine (I) at amino acid position 776 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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not provided
(-)
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no classification provided
Method: phenotyping only
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Autosomal dominant limb-girdle muscular dystrophy type 1F
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV004228948.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
Variant interpreted as Uncertain significance and reported on 07-24-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the … (more)
Variant interpreted as Uncertain significance and reported on 07-24-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormal lens morphology (present) , Abnormality of vision (present)
Indication for testing: Diagnostic
Age: 50-59 years
Sex: female
Method: Gene Panel Sequencing
Testing laboratory: Invitae
Date variant was reported to submitter: 2019-07-24
Testing laboratory interpretation: Uncertain significance
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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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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TNPO3 | - | - | - | - |
Text-mined citations for rs368873021 ...
HelpRecord last updated May 01, 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.