ClinVar Genomic variation as it relates to human health
NM_152618.3(BBS12):c.1502C>T (p.Thr501Met)
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_152618.3(BBS12):c.1502C>T (p.Thr501Met)
Variation ID: 585190 Accession: VCV000585190.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 4q27 4: 122743394 (GRCh38) [ NCBI UCSC ] 4: 123664549 (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 Jan 12, 2019 Feb 14, 2024 Jan 14, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152618.3:c.1502C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689831.2:p.Thr501Met missense NM_001178007.2:c.1502C>T NP_001171478.1:p.Thr501Met missense NC_000004.12:g.122743394C>T NC_000004.11:g.123664549C>T NG_021203.1:g.15693C>T - Protein change
- T501M
- Other names
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- Canonical SPDI
- NC_000004.12:122743393: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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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00004
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Trans-Omics for Precision Medicine (TOPMed) 0.00019
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00020
1000 Genomes Project 30x 0.00031
- 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 | ||
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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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BBS12 | - | - |
GRCh38 GRCh37 |
726 | 752 |
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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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 14, 2024 | RCV000735937.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Mar 26, 2019 | RCV001075675.2 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Oct 25, 2023 | RCV001784348.9 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Dec 16, 2022 | RCV003235371.1 |
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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Likely pathogenic
(Mar 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001241303.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
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Pathogenic
(May 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002547701.1
First in ClinVar: Jul 17, 2022 Last updated: Jul 17, 2022 |
Comment:
Variant summary: BBS12 c.1502C>T (p.Thr501Met) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: BBS12 c.1502C>T (p.Thr501Met) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251444 control chromosomes. c.1502C>T has been reported in the literature in multiple individuals affected with Bardet-Biedl Syndrome. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and showed that mutant protein with p.T501M was significantly different to control in an in vivo assay (Zaghloul_2010). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Apr 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002796418.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(Dec 16, 2022)
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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: SCV003933037.1
First in ClinVar: Jun 24, 2023 Last updated: Jun 24, 2023 |
Comment:
Published functional studies suggest a damaging effect (Zaghloul et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein … (more)
Published functional studies suggest a damaging effect (Zaghloul et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17160889, 30614526, 20472660, 20498079) (less)
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Pathogenic
(Jan 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
germline
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New York Genome Center
Accession: SCV004046482.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Clinical Features:
Hyperlipidemia (present) , Type 2 diabetes mellitus (present)
Secondary finding: no
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Pathogenic
(Oct 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211657.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Oct 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 12
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022017.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 14, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000932058.5
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 501 of the BBS12 protein (p.Thr501Met). … (more)
This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 501 of the BBS12 protein (p.Thr501Met). This variant is present in population databases (rs138011813, gnomAD 0.05%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 17160889, 20472660). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 585190). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BBS12 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects BBS12 function (PMID: 20080638, 20498079). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 15, 2018)
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no assertion criteria provided
Method: provider interpretation
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Bardet-Biedl syndrome
Affected status: yes
Allele origin:
germline
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Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University
Study: French fetal BBS cohort
Accession: SCV000839575.1 First in ClinVar: Jan 12, 2019 Last updated: Jan 12, 2019 |
Age: 20-29 weeks gestation
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Pathogenic
(Jul 23, 2020)
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome type 12
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002084739.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Bardet-Biedl syndrome: Antenatal presentation of forty-five fetuses with biallelic pathogenic variants in known Bardet-Biedl syndrome genes. | Mary L | Clinical genetics | 2019 | PMID: 30614526 |
Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity. | Braun DA | Kidney international | 2016 | PMID: 26489029 |
BBS mutational analysis: a strategic approach. | Billingsley G | Ophthalmic genetics | 2011 | PMID: 21463199 |
Functional analyses of variants reveal a significant role for dominant negative and common alleles in oligogenic Bardet-Biedl syndrome. | Zaghloul NA | Proceedings of the National Academy of Sciences of the United States of America | 2010 | PMID: 20498079 |
Mutations in chaperonin-like BBS genes are a major contributor to disease development in a multiethnic Bardet-Biedl syndrome patient population. | Billingsley G | Journal of medical genetics | 2010 | PMID: 20472660 |
BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. | Seo S | Proceedings of the National Academy of Sciences of the United States of America | 2010 | PMID: 20080638 |
Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. | Stoetzel C | American journal of human genetics | 2007 | PMID: 17160889 |
Text-mined citations for rs138011813 ...
HelpRecord last updated May 08, 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.