NM_000352.6(ABCC8):c.3517G>A (p.Val1173Met) AND Monogenic diabetes

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001249021.10

Allele description [Variation Report for NM_000352.6(ABCC8):c.3517G>A (p.Val1173Met)]

NM_000352.6(ABCC8):c.3517G>A (p.Val1173Met)

Gene:

ABCC8:ATP binding cassette subfamily C member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000352.6(ABCC8):c.3517G>A (p.Val1173Met)

HGVS:

NC_000011.10:g.17404552C>T
NG_008867.1:g.77351G>A
NM_000352.4:c.3517G>A
NM_000352.6:c.3517G>AMANE SELECT
NM_001287174.3:c.3520G>A
NM_001351295.2:c.3583G>A
NM_001351296.2:c.3517G>A
NM_001351297.2:c.3514G>A
NP_000343.2:p.Val1173Met
NP_001274103.1:p.Val1174Met
NP_001338224.1:p.Val1195Met
NP_001338225.1:p.Val1173Met
NP_001338226.1:p.Val1172Met
LRG_790t1:c.3517G>A
LRG_790t2:c.3520G>A
LRG_790:g.77351G>A
LRG_790p1:p.Val1173Met
LRG_790p2:p.Val1174Met
NC_000011.9:g.17426099C>T
NM_000352.3:c.3517G>A
NM_000352.4(ABCC8):c.3517G>A
NM_000352.6:c.3517G>A
NM_001287174.1:c.3520G>A
NR_147094.2:n.3666G>A

Protein change:

V1172M

Links:

dbSNP: rs141322087

NCBI 1000 Genomes Browser:

rs141322087

Molecular consequence:

NM_000352.6:c.3517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.3520G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.3583G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.3517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.3514G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.3666G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Monogenic diabetes
Identifiers:: MONDO: MONDO:0015967; MedGen: C3888631

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001422928	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 22, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001422928

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 22, 2020)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001422928.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

The p.Val1173Met variant in ABCC8 has been reported in 1 individual with Monogenic Diabetes in ClinVar (Variation ID: 35609), and has been identified in 0.003098% (4/129110) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs141322087). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a carrier frequency. Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. This variant has also been reported likely pathogenic in ClinVar (Variation ID: 35609). Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Val1173Met variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, BP4 (Richards 2015).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

ClinVar

Relating variation to medicine