ClinVar Genomic variation as it relates to human health
NM_170784.3(MKKS):c.1015A>G (p.Ile339Val)
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(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_170784.3(MKKS):c.1015A>G (p.Ile339Val)
Variation ID: 100586 Accession: VCV000100586.30
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 20p12.2 20: 10408774 (GRCh38) [ NCBI UCSC ] 20: 10389422 (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 Feb 25, 2014 Apr 15, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_170784.3:c.1015A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_740754.1:p.Ile339Val missense NM_018848.3:c.1015A>G NP_061336.1:p.Ile339Val missense NR_072977.2:n.376A>G non-coding transcript variant NC_000020.11:g.10408774T>C NC_000020.10:g.10389422T>C NG_009109.2:g.30445A>G Q9NPJ1:p.Ile339Val - Protein change
- I339V
- Other names
- BBS6
- NM_018848.3(MKKS):c.1015A>G(p.Ile339Val)
- NM_170784.2(MKKS):c.1015A>G(p.Ile339Val)
- Canonical SPDI
- NC_000020.11:10408773:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- unknown functional consequence
-
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.
-
0.00220 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00219
1000 Genomes Project 0.00220
Trans-Omics for Precision Medicine (TOPMed) 0.00290
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00300
The Genome Aggregation Database (gnomAD) 0.00359
The Genome Aggregation Database (gnomAD), exomes 0.00422
Exome Aggregation Consortium (ExAC) 0.00438
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. |
|||
MKKS | - | - |
GRCh38 GRCh37 |
527 | 581 |
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. |
---|---|---|---|---|
Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Jan 1, 2024 | RCV000086969.23 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Apr 5, 2017 | RCV000173033.27 | |
Benign (1) |
criteria provided, single submitter
|
Jan 31, 2024 | RCV001083442.12 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
May 28, 2019 | RCV000585746.16 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
May 31, 2018 | RCV000677321.15 |
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
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
McKusick-Kaufman syndrome
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001141213.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
Likely benign
(Feb 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000520964.6
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 22025579, 22090721, 29221435, 18094050, 20498079, 12107442, 15770229, 29127258, 29343940, 20177705)
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000313269.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
Likely benign
(Apr 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000595790.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
Benign
(May 31, 2018)
|
criteria provided, single submitter
Method: curation
|
Bardet-Biedl syndrome 6
Affected status: unknown
Allele origin:
unknown
|
SIB Swiss Institute of Bioinformatics
Accession: SCV000803528.1
First in ClinVar: Aug 20, 2018 Last updated: Aug 20, 2018 |
Comment:
This variant is interpreted as a Benign, for Bardet-biedl syndrome 6, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines … (more)
This variant is interpreted as a Benign, for Bardet-biedl syndrome 6, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. (less)
|
|
Likely benign
(Jan 17, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000203022.7
First in ClinVar: Feb 02, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 3
Sex: mixed
|
|
Uncertain significance
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
McKusick-Kaufman syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001303009.1
First in ClinVar: May 31, 2020 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
|
|
Uncertain significance
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Bardet-Biedl syndrome 6
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001303010.1
First in ClinVar: May 31, 2020 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
|
|
Benign
(Sep 23, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000297289.3
First in ClinVar: Jul 31, 2016 Last updated: Dec 24, 2022 |
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
McKusick-Kaufman syndrome
Bardet-Biedl syndrome
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000557436.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
|
|
Likely benign
(Jan 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004149869.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
MKKS: BP4, BS2
Number of individuals with the variant: 11
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001920145.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: research
|
McKusick-Kaufman syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
|
Tolun Lab, Human Genetics Laboratory, Bogazici University
Accession: SCV000583517.1
First in ClinVar: Mar 09, 2018 Last updated: Mar 09, 2018 |
Number of individuals with the variant: 5
Clinical Features:
Polydactyly (present) , Intellectual disability (present) , Obesity (present) , Rod-cone dystrophy (present)
Age: 16-26 years
Sex: mixed
Ethnicity/Population group: Pakistani
Geographic origin: Pakistan
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001928163.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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: SCV001954392.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV001973116.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
|
|
not provided
(-)
|
no classification provided
Method: not provided
|
not provided
Affected status: not provided
Allele origin:
not provided
|
NEI Ophthalmic Genomics Laboratory, National Institutes of Health
Accession: SCV000119222.1
First in ClinVar: Feb 25, 2014 Last updated: Feb 25, 2014 |
|
|
click to load more click to collapse |
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
---|---|---|---|---|
unknown functional consequence
|
|
|
Tolun Lab, Human Genetics Laboratory, Bogazici University
Accession: SCV000583517.1
|
|
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly. | Yıldız Bölükbaşı E | Journal of medical genetics | 2018 | PMID: 29127258 |
MKKS is a centrosome-shuttling protein degraded by disease-causing mutations via CHIP-mediated ubiquitination. | Hirayama S | Molecular biology of the cell | 2008 | PMID: 18094050 |
Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients. | Slavotinek AM | Human genetics | 2002 | PMID: 12107442 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MKKS | - | - | - | - |
Text-mined citations for rs137853909 ...
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.