VCV000553787.3 - ClinVar

NM_000352.6(ABCC8):c.3399+1G>A

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Likely pathogenic(2); Uncertain significance(2)

4 out of 4 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000352.6(ABCC8):c.3399+1G>A

Variation ID: 553787 Accession: VCV000553787.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.1 11: 17405493 (GRCh38) [ NCBI UCSC ] 11: 17427040 (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	Aug 5, 2018	Dec 30, 2023	Apr 17, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000352.6:c.3399+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_001287174.3:c.3402+1G>A		splice donor
NM_001351295.2:c.3465+1G>A		splice donor
NM_001351296.2:c.3399+1G>A		splice donor
NM_001351297.2:c.3396+1G>A		splice donor
NC_000011.10:g.17405493C>T
NC_000011.9:g.17427040C>T
NG_008867.1:g.76410G>A
LRG_790:g.76410G>A
LRG_790t1:c.3399+1G>A
LRG_790t2:c.3402+1G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000011.10:17405492:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA379799996 dbSNP: rs1554911369 VarSome

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
Gene	OMIM	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.
ABCC8		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	2580	2724

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.
Hyperinsulinemic hypoglycemia, familial, 1	Likely pathogenic (1)	criteria provided, single submitter	Nov 14, 2017	RCV000669304.1
Transitory neonatal diabetes mellitus	Uncertain significance (1)	criteria provided, single submitter	-	RCV002245556.2
Maturity onset diabetes mellitus in young	Uncertain significance (1)	criteria provided, single submitter	-	RCV002245555.2
Type 2 diabetes mellitus	Likely pathogenic (1)	criteria provided, single submitter	Apr 17, 2023	RCV003472114.1

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.
Likely pathogenic (Nov 14, 2017) C Contributing to aggregate classification	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Hyperinsulinemic hypoglycemia, familial, 1 Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000794046.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1) Method: research	Transitory neonatal diabetes mellitus (Somatic mutation) Affected status: unknown Allele origin: somatic	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV002515476.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022	Publications: PubMed (8) PubMed: 16885549‚ 21989597‚ 27538677‚ 18981553‚ 32027066‚ 16613899‚ 18025408‚ 32792356 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 ( rs1554911369) in neonatal diabetes yet. (less)
Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1) Method: research	Maturity onset diabetes mellitus in young (Somatic mutation) Affected status: unknown Allele origin: somatic	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV002515477.1 First in ClinVar: May 21, 2022 Last updated: May 21, 2022	Publications: PubMed (8) PubMed: 16885549‚ 21989597‚ 27538677‚ 18981553‚ 32027066‚ 16613899‚ 18025408‚ 32792356 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 ( rs1554911369) in MODY yet. (less)
Likely pathogenic (Apr 17, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Type 2 diabetes mellitus Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004201446.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023

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 sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs1554911369) in neonatal diabetes yet.

Comment:

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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
Permanent neonatal diabetes mellitus due to a C96Y heterozygous mutation in the insulin gene. A case report.	Ahamed A	JOP : Journal of the pancreas	2008	PMID: 18981553
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 rs1554911369 ...

These 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 Mar 16, 2025

ClinVar Genomic variation as it relates to human health

NM_000352.6(ABCC8):c.3399+1G>A

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1554911369 ...