ClinVar Genomic variation as it relates to human health
NM_000352.6(ABCC8):c.3975C>T (p.Tyr1325=)
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); Benign(2); Likely benign(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000352.6(ABCC8):c.3975C>T (p.Tyr1325=)
Variation ID: 303756 Accession: VCV000303756.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.1 11: 17397206 (GRCh38) [ NCBI UCSC ] 11: 17418753 (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 Mar 10, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000352.6:c.3975C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000343.2:p.Tyr1325= synonymous NM_001287174.3:c.3978C>T NP_001274103.1:p.Tyr1326= synonymous NM_001351295.2:c.4041C>T NP_001338224.1:p.Tyr1347= synonymous NM_001351296.2:c.3975C>T NP_001338225.1:p.Tyr1325= synonymous NM_001351297.2:c.3972C>T NP_001338226.1:p.Tyr1324= synonymous NR_147094.2:n.4124C>T non-coding transcript variant NC_000011.10:g.17397206G>A NC_000011.9:g.17418753G>A NG_008867.1:g.84697C>T LRG_790:g.84697C>T LRG_790t1:c.3975C>T LRG_790p1:p.Tyr1325= LRG_790t2:c.3978C>T LRG_790p2:p.Tyr1326= - Protein change
- Other names
- -
- Canonical SPDI
- NC_000011.10:17397205:G:A
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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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0.00120 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00121
Trans-Omics for Precision Medicine (TOPMed) 0.00125
The Genome Aggregation Database (gnomAD), exomes 0.00039
Exome Aggregation Consortium (ExAC) 0.00050
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00108
1000 Genomes Project 0.00120
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
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. |
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ABCC8 | - | - |
GRCh38 GRCh37 |
2296 | 2422 |
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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Likely benign (1) |
criteria provided, single submitter
|
Jan 13, 2018 | RCV000299357.7 | |
Benign (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV000340284.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 13, 2018 | RCV000401324.7 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 6, 2017 | RCV000501079.7 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000872611.21 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV002246117.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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- | RCV002246116.3 | |
Likely benign (1) |
criteria provided, single submitter
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Sep 10, 2022 | RCV002374518.2 |
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
(Dec 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000592963.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Likely benign
(Feb 06, 2017)
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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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Athena Diagnostics Inc
Accession: SCV000612212.1
First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017 |
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Likely benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Permanent neonatal diabetes mellitus 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000369257.3
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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Diabetes mellitus, transient neonatal, 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000369258.3
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)
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Uncertain significance
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hyperinsulinemic hypoglycemia, familial, 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000369259.3
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Likely benign
(Jul 01, 2019)
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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: SCV001783524.1
First in ClinVar: Aug 14, 2021 Last updated: Aug 14, 2021 |
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Uncertain significance
(-)
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criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
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Transitory neonatal diabetes mellitus
(Somatic mutation)
Affected status: unknown
Allele origin:
somatic
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Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002513524.1
First in ClinVar: May 24, 2022 Last updated: May 24, 2022 |
Comment:
Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to … (more)
Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant (rs138141427) in neonatal diabetes yet. (less)
|
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Uncertain significance
(-)
|
criteria provided, single submitter
(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)
Method: research
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Maturity onset diabetes mellitus in young
(Somatic mutation)
Affected status: unknown
Allele origin:
somatic
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Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic
Accession: SCV002513523.1
First in ClinVar: May 24, 2022 Last updated: May 24, 2022 |
Comment:
Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to … (more)
Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant (rs138141427) in MODY yet. (less)
|
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Likely benign
(Sep 10, 2022)
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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: SCV002625096.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Benign
(Jan 29, 2024)
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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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Invitae
Accession: SCV001014455.7
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
|
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Likely benign
(Sep 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002585318.8
First in ClinVar: Oct 22, 2022 Last updated: Mar 10, 2024 |
Comment:
ABCC8: BP4, BP7
Number of individuals with the variant: 1
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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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Molecular and clinical characteristics of monogenic diabetes mellitus in southern Chinese children with onset before 3 years of age. | Lin Y | BMJ open diabetes research & care | 2020 | PMID: 32792356 |
Update of variants identified in the pancreatic β-cell K(ATP) channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes. | De Franco E | Human mutation | 2020 | PMID: 32027066 |
ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective. | Ovsyannikova AK | Diabetes therapy : research, treatment and education of diabetes and related disorders | 2016 | PMID: 27538677 |
Heterozygous ABCC8 mutations are a cause of MODY. | Bowman P | Diabetologia | 2012 | PMID: 21989597 |
Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. | Rafiq M | Diabetes care | 2008 | PMID: 18025408 |
Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. | Babenko AP | The New England journal of medicine | 2006 | PMID: 16885549 |
A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. | Proks P | Human molecular genetics | 2006 | PMID: 16613899 |
Text-mined citations for rs138141427 ...
HelpRecord last updated Mar 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.