NM_000352.6(ABCC8):c.4591A>G (p.Thr1531Ala) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 28, 2021
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:: RCV001818022.4

Allele description [Variation Report for NM_000352.6(ABCC8):c.4591A>G (p.Thr1531Ala)]

NM_000352.6(ABCC8):c.4591A>G (p.Thr1531Ala)

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.4591A>G (p.Thr1531Ala)

HGVS:

NC_000011.10:g.17393714T>C
NG_008867.1:g.88189A>G
NM_000352.6:c.4591A>GMANE SELECT
NM_001287174.3:c.4594A>G
NM_001351295.2:c.4657A>G
NM_001351296.2:c.4591A>G
NM_001351297.2:c.4588A>G
NP_000343.2:p.Thr1531Ala
NP_001274103.1:p.Thr1532Ala
NP_001338224.1:p.Thr1553Ala
NP_001338225.1:p.Thr1531Ala
NP_001338226.1:p.Thr1530Ala
LRG_790t1:c.4591A>G
LRG_790t2:c.4594A>G
LRG_790:g.88189A>G
LRG_790p1:p.Thr1531Ala
LRG_790p2:p.Thr1532Ala
NC_000011.9:g.17415261T>C
NM_000352.4:c.4591A>G
NR_147094.2:n.4886A>G

Protein change:

T1530A

Links:

dbSNP: rs796891223

NCBI 1000 Genomes Browser:

rs796891223

Molecular consequence:

NM_000352.6:c.4591A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.4594A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.4657A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.4591A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.4588A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.4886A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002065855	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002065855

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 28, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

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 Genetic Services Laboratory, University of Chicago, SCV002065855.1

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

Description

DNA sequence analysis of the ABCC8 gene demonstrated a sequence change, c.4591A>G, in exon 38 that results in an amino acid change, p.Thr1531Ala. This sequence change has not been described in population database including gnomAD. The p.Thr1531Ala change affects a highly conserved amino acid residue located in a domain of the ABCC8 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Thr1531Ala substitution. This sequence change has previously been reported in the compound heterozygous state with another ABCC8 variant in an individual with congenital hyperinsulinism (PMID: 19475716). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr1531Ala change remains unknown at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine