NM_001171.6(ABCC6):c.3421C>T (p.Arg1141Ter) AND ABCC6-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 22, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002291267.5

Allele description [Variation Report for NM_001171.6(ABCC6):c.3421C>T (p.Arg1141Ter)]

NM_001171.6(ABCC6):c.3421C>T (p.Arg1141Ter)

Gene:

ABCC6:ATP binding cassette subfamily C member 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.11

Genomic location:

Preferred name:

NM_001171.6(ABCC6):c.3421C>T (p.Arg1141Ter)

HGVS:

NC_000016.10:g.16163078G>A
NG_007558.3:g.65540C>T
NM_001171.6:c.3421C>TMANE SELECT
NM_001351800.1:c.3079C>T
NP_001162.4:p.Arg1141Ter
NP_001162.5:p.Arg1141Ter
NP_001338729.1:p.Arg1027Ter
LRG_1115t1:c.3421C>T
LRG_1115:g.65540C>T
LRG_1115p1:p.Arg1141Ter
NC_000016.9:g.16256935G>A
NG_007558.2:g.65394C>T
NM_001171.5:c.3421C>T

Protein change:

R1027*; ARG1141TER

Links:

OMIM: 603234.0001; dbSNP: rs72653706

NCBI 1000 Genomes Browser:

rs72653706

Molecular consequence:

NM_001171.6:c.3421C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351800.1:c.3079C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: ABCC6-related disorder
Synonyms:: ABCC6-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002583665	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 30, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004112191	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 22, 2023)	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

SCV002583665

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 30, 2022)

germline

clinical testing

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

SCV004112191

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 22, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	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 Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV002583665.1

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

Description

PVS1, PS3, PM3_Strong

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

From PreventionGenetics, part of Exact Sciences, SCV004112191.1

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

Description

The ABCC6 c.3421C>T variant is predicted to result in premature protein termination (p.Arg1141*). This variant has been reported to be causative for autosomal recessive pseudoxanthoma elasticum (PXE) (Ringpfeil et al. 2000. PubMed ID: 10811882, ABCC6 gene was reported as MRP6 gene; Hu et al. 2003. PubMed ID: 12714611; Miksch et al. 2005. PubMed ID: 16086317). In addition, several studies have reported a significantly increased risk of coronary artery disease in carriers of the ABCC6 p.Arg1141* variant (Trip et al. 2002. PubMed ID: 12176944; Köblös et al. 2010. PubMed ID: 19929409). Nonsense variants in ABCC6 are expected to be pathogenic. This variant is interpreted as pathogenic.

#	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: Jun 17, 2024

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