ClinVar Genomic variation as it relates to human health
NM_003413.4(ZIC3):c.49G>T (p.Gly17Cys)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_003413.4(ZIC3):c.49G>T (p.Gly17Cys)
Variation ID: 190129 Accession: VCV000190129.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq26.3 X: 137566740 (GRCh38) [ NCBI UCSC ] X: 136648899 (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 Nov 12, 2015 Aug 4, 2024 Jul 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003413.4:c.49G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003404.1:p.Gly17Cys missense NM_001330661.1:c.49G>T NP_001317590.1:p.Gly17Cys missense NC_000023.11:g.137566740G>T NC_000023.10:g.136648899G>T NG_008115.2:g.5614G>T O60481:p.Gly17Cys - Protein change
- G17C
- Other names
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- Canonical SPDI
- NC_000023.11:137566739: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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0.00079 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00062
1000 Genomes Project 0.00079
Trans-Omics for Precision Medicine (TOPMed) 0.00164
The Genome Aggregation Database (gnomAD) 0.00206
The Genome Aggregation Database (gnomAD), exomes 0.00259
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00295
Exome Aggregation Consortium (ExAC) 0.00507
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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ZIC3 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
150 | 319 |
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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Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jun 2, 2016 | RCV000248648.9 | |
Likely benign (2) |
criteria provided, single submitter
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Apr 28, 2017 | RCV000201846.10 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000360572.5 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jan 22, 2024 | RCV000198780.17 | |
Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Jul 1, 2024 | RCV001563202.12 |
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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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Congenital heart defects 1, nonsyndromic, 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000481805.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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X-linked Heterotaxy, Visceral, 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000481806.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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VACTERL association, X-linked, with or without hydrocephalus
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000481807.3
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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Likely benign
(Mar 03, 2015)
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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: SCV001786102.1
First in ClinVar: Aug 14, 2021 Last updated: Aug 14, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 26294094, 19933292, 24123890, 23427188)
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Benign
(-)
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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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PreventionGenetics, part of Exact Sciences
Accession: SCV000309582.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(Jun 02, 2016)
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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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000540697.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1% frequency and 26 hemizygotes in the European population in ExAC (less)
Method: Genome/Exome Filtration
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Likely benign
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Heterotaxy, visceral, 1, X-linked
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767260.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as likely benign. Following criteria are met: 0308 - Population frequency for this variant is out of keeping with known incidence of X-linked recessive Congenital heart defects, nonsyndromic, 1 (MIM#306955). (SB) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Benign
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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Heterotaxy, visceral, 1, X-linked
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000252781.11
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
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Benign
(Jan 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Heterotaxy, visceral, 1, X-linked
Affected status: no
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440737.1
First in ClinVar: Oct 30, 2020 Last updated: Oct 30, 2020 |
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Likely benign
(Jul 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004165731.8
First in ClinVar: Nov 20, 2023 Last updated: Aug 04, 2024 |
Comment:
ZIC3: BS1
Number of individuals with the variant: 8
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799290.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
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: SCV001928927.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965152.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Pathogenic
(Jan 01, 2015)
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Flagged submission
flagged submission
Method: research
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
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VACTERL association, X-linked, with or without hydrocephalus
Affected status: yes
Allele origin:
maternal
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Reutter Lab, Institute of Human Genetics, University Hospital Bonn
Study: Systematic search for genes to be involved in the VACTER/VACTERL association
Accession: SCV000222773.1 First in ClinVar: Nov 12, 2015 Last updated: Nov 12, 2015
Comment:
molecular genetic
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Number of individuals with the variant: 4
Family history: yes
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
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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Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association. | Hilger AC | Human mutation | 2015 | PMID: 26294094 |
[Characteristics of the formation of conditioned responses in the isolated LPa3 neuron of the edible snail]. | Grechenko TN | Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova | 1989 | PMID: 2629409 |
Text-mined citations for rs147232392 ...
HelpRecord last updated Aug 11, 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.