NM_001171.6(ABCC6):c.3904G>A (p.Gly1302Arg) AND Autosomal recessive inherited pseudoxanthoma elasticum

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Apr 4, 2024
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:: RCV000006957.11

Allele description [Variation Report for NM_001171.6(ABCC6):c.3904G>A (p.Gly1302Arg)]

NM_001171.6(ABCC6):c.3904G>A (p.Gly1302Arg)

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.3904G>A (p.Gly1302Arg)

HGVS:

NC_000016.10:g.16155010C>T
NG_007558.3:g.73608G>A
NM_001171.6:c.3904G>AMANE SELECT
NM_001351800.1:c.3562G>A
NP_001162.4:p.Gly1302Arg
NP_001162.5:p.Gly1302Arg
NP_001338729.1:p.Gly1188Arg
LRG_1115t1:c.3904G>A
LRG_1115:g.73608G>A
LRG_1115p1:p.Gly1302Arg
NC_000016.9:g.16248867C>T
NG_007558.2:g.73462G>A
NM_001171.5:c.3904G>A
NR_147784.1:n.3566G>A
O95255:p.Gly1302Arg

Protein change:

G1188R; GLY1302ARG

Links:

UniProtKB: O95255#VAR_013386; OMIM: 603234.0020; dbSNP: rs63749856

NCBI 1000 Genomes Browser:

rs63749856

Molecular consequence:

NM_001171.6:c.3904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351800.1:c.3562G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_147784.1:n.3566G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal recessive inherited pseudoxanthoma elasticum (PXE)
Synonyms:: Gronblad Strandberg syndrome
Identifiers:: MONDO: MONDO:0009925; MedGen: C1275116; Orphanet: 758; OMIM: 264800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000027153	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2002)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 12384774, 11880368
SCV000589086	PXE International	no assertion criteria provided	Pathogenic (Mar 1, 2021)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV000607216	GenomeConnect, ClinGen	no classification provided	not provided	unknown	phenotyping only
SCV004809525	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 4, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	4	not provided	not provided	4	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	phenotyping only
.	germline	yes	3	not provided	not provided	3	not provided	research
Causasians	germline	yes	6	not provided	not provided	6	not provided	research

Citations

PubMed

Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa.

Le Saux O, Beck K, Sachsinger C, Treiber C, Göring HH, Curry K, Johnson EW, Bercovitch L, Marais AS, Terry SF, Viljoen DL, Boyd CD.

Hum Genet. 2002 Oct;111(4-5):331-8. Epub 2002 Sep 7.

PubMed [citation]

PMID:: 12384774

Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6).

Iliás A, Urbán Z, Seidl TL, Le Saux O, Sinkó E, Boyd CD, Sarkadi B, Váradi A.

J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5.

PubMed [citation]

PMID:: 11880368

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000027153.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a cohort of 122 unrelated patients with pseudoxanthoma elasticum (PXE; 264800) from several countries, Le Saux et al. (2001) found a 3904G-A transition in exon 28 of the ABCC6 gene that resulted in a gly1302-to-arg (G1302R) amino acid substitution in the second intracellular nucleotide-binding domain. The mutation, present in homozygosity, occurred in a total of 4 alleles from patients from the United States, giving an allele frequency of 5.4% in a total of 74 United States alleles. It was not found in the European population.

Ilias et al. (2002) showed that the G1302R mutation did not affect the expression of the ABCC6 protein in infected insect cells, but that the protein was essentially inactive in the MgATP-dependent transport of N-ethylmaleimide S-glutathione (NEM-GS) or leukotriene-C4.

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

From PXE International, SCV000589086.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)
2	not provided	1	not provided	not provided	research	PubMed (1)
3	not provided	1	not provided	not provided	research	PubMed (1)
4	not provided	1	not provided	not provided	research	PubMed (1)
5	.	1	not provided	not provided	research	PubMed (1)
6	.	1	not provided	not provided	research	PubMed (1)
7	.	1	not provided	not provided	research	PubMed (1)
8	Causasians	1	not provided	not provided	research	PubMed (1)
9	Causasians	1	not provided	not provided	research	PubMed (1)
10	Causasians	1	not provided	not provided	research	PubMed (1)
11	Causasians	1	not provided	not provided	research	PubMed (1)
12	Causasians	1	not provided	not provided	research	PubMed (1)
13	Causasians	1	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
2	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
3	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
4	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
5	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
6	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
7	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
8	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
9	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
10	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
11	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
12	germline	yes	1	blood	not provided		1	not provided	not provided	not provided
13	germline	yes	1	blood	not provided		1	not provided	not provided	not provided

From GenomeConnect, ClinGen, SCV000607216.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004809525.1

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

#	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: Oct 13, 2024

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