NM_001171.6(ABCC6):c.3490C>T (p.Arg1164Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 29, 2024
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:: RCV000255402.13

Allele description [Variation Report for NM_001171.6(ABCC6):c.3490C>T (p.Arg1164Ter)]

NM_001171.6(ABCC6):c.3490C>T (p.Arg1164Ter)

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.3490C>T (p.Arg1164Ter)

HGVS:

NC_000016.10:g.16163009G>A
NG_007558.3:g.65609C>T
NM_001171.6:c.3490C>TMANE SELECT
NM_001351800.1:c.3148C>T
NP_001162.4:p.Arg1164Ter
NP_001162.5:p.Arg1164Ter
NP_001338729.1:p.Arg1050Ter
LRG_1115t1:c.3490C>T
LRG_1115:g.65609C>T
LRG_1115p1:p.Arg1164Ter
NC_000016.9:g.16256866G>A
NG_007558.2:g.65463C>T
NM_001171.5:c.3490C>T
p.Arg1164X

Protein change:

R1050*; ARG1164TER

Links:

OMIM: 603234.0013; dbSNP: rs72653744

NCBI 1000 Genomes Browser:

rs72653744

Molecular consequence:

NM_001171.6:c.3490C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351800.1:c.3148C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000321367	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (May 9, 2023)	germline	clinical testing	Citation Link,
SCV002018595	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 29, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002137652	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11536079, 17617515, 11179012, 11439001, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000321367

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(May 9, 2023)

germline

clinical testing

Citation Link,

SCV002018595

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 29, 2023)

germline

clinical testing

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

SCV002137652

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 29, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum.

Le Saux O, Beck K, Sachsinger C, Silvestri C, Treiber C, Göring HH, Johnson EW, De Paepe A, Pope FM, Pasquali-Ronchetti I, Bercovitch L, Marais AS, Viljoen DL, Terry SF, Boyd CD.

Am J Hum Genet. 2001 Oct;69(4):749-64. Epub 2001 Aug 31. Erratum in: Am J Hum Genet 2001 Dec;69(6):1413. Am J Hum Genet 2002 Aug;71(2):448.

PubMed [citation]

PMID:: 11536079
PMCID:: PMC1226061

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000321367.8

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

Description

Reported in the heterozygous state in three patients with pseudoxanthoma elasticum from two families, although a second ABCC6 variant was not identified in these cases (Meloni et al., 2001; Chassaing et al., 2004); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 1179012, 25525159, 28696355, 34205333, 34906475, 33879512, 31980526, 17617515, 11179012, 30056620, 29948180, 31269855, 30879837, 15086542, 28186352, 11439001, 10954200, 29480367, 31589614, 31345219)

#	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 Revvity Omics, Revvity, SCV002018595.3

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002137652.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg1164*) in the ABCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCC6 are known to be pathogenic (PMID: 11536079, 17617515). This variant is present in population databases (rs72653744, gnomAD 0.07%). This premature translational stop signal has been observed in individuals with pseudoxanthoma elasticum (PMID: 11179012, 11439001). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6572). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified 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: Oct 13, 2024

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