Gly43Gly in exon 2 of PAX3: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 15.5% (682/4396) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12623857).
ClinVar Genomic variation as it relates to human health
NM_181458.4(PAX3):c.129T>C (p.Gly43=)
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.
(13)
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.
Benign
13
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_181458.4(PAX3):c.129T>C (p.Gly43=)
Variation ID: 195432 Accession: VCV000195432.25
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q36.1 2: 222297170 (GRCh38) [ NCBI UCSC ] 2: 223161889 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 2, 2016 Sep 29, 2024 Jan 31, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_181458.4:c.129T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_852123.1:p.Gly43= synonymous NM_000438.6:c.129T>C NP_000429.2:p.Gly43= synonymous NM_001127366.3:c.129T>C NP_001120838.1:p.Gly43= synonymous NM_013942.5:c.129T>C NP_039230.1:p.Gly43= synonymous NM_181457.4:c.129T>C NP_852122.1:p.Gly43= synonymous NM_181459.4:c.129T>C NP_852124.1:p.Gly43= synonymous NM_181460.4:c.129T>C NP_852125.1:p.Gly43= synonymous NM_181461.4:c.129T>C NP_852126.1:p.Gly43= synonymous NC_000002.12:g.222297170A>G NC_000002.11:g.223161889A>G NG_011632.1:g.6812T>C NG_021186.1:g.4024A>G - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000002.12:222297169:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.09565 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.84653
The Genome Aggregation Database (gnomAD) 0.84982
Trans-Omics for Precision Medicine (TOPMed) 0.85934
The Genome Aggregation Database (gnomAD), exomes 0.88424
Exome Aggregation Consortium (ExAC) 0.88715
1000 Genomes Project 30x 0.89944
1000 Genomes Project 0.90435
- 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. |
|||
| PAX3 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
303 | 401 | |
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. |
|---|---|---|---|---|
| Benign (6) |
criteria provided, multiple submitters, no conflicts
|
May 9, 2017 | RCV000176002.18 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV000326158.5 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 5, 2021 | RCV000362250.7 | |
| Benign (1) |
criteria provided, single submitter
|
Sep 5, 2021 | RCV001788058.2 | |
| Benign (1) |
criteria provided, single submitter
|
Sep 5, 2021 | RCV001788059.2 | |
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV002056946.6 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000316719.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Aug 04, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000227582.5
First in ClinVar: Jun 29, 2015 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Benign
(Nov 24, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000269608.3
First in ClinVar: May 29, 2016 Last updated: Apr 09, 2018 |
Comment:
Gly43Gly in exon 2 of PAX3: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue … (more)
Gly43Gly in exon 2 of PAX3: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 15.5% (682/4396) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12623857). (less)
Number of individuals with the variant: 1027
|
|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Craniofacial-deafness-hand syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000427911.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(Jan 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Waardenburg syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000427910.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(May 09, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000717032.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
|
Benign
(Sep 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Waardenburg syndrome type 3
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002029393.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
|
|
|
Benign
(Sep 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Craniofacial-deafness-hand syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002029391.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
|
|
|
Benign
(Sep 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Waardenburg syndrome type 1
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002029392.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
|
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002408806.3
First in ClinVar: Apr 08, 2022 Last updated: Feb 20, 2024 |
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005240509.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001740344.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953492.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
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:
Gly43Gly in exon 2 of PAX3: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 15.5% (682/4396) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12623857).
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PAX3 | - | - | - | - |
Text-mined citations for rs12623857 ...
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 Sep 29, 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.