ClinVar Genomic variation as it relates to human health
NM_001171.6(ABCC6):c.4198G>A (p.Glu1400Lys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001171.6(ABCC6):c.4198G>A (p.Glu1400Lys)
Variation ID: 433353 Accession: VCV000433353.6
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16p13.11 16: 16154638 (GRCh38) [ NCBI UCSC ] 16: 16248495 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 27, 2017 Feb 14, 2024 May 10, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001171.6:c.4198G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001162.5:p.Glu1400Lys missense NM_001351800.1:c.3856G>A NP_001338729.1:p.Glu1286Lys missense NR_147784.1:n.3860G>A non-coding transcript variant NC_000016.10:g.16154638C>T NC_000016.9:g.16248495C>T NG_007558.3:g.73980G>A LRG_1115:g.73980G>A LRG_1115t1:c.4198G>A LRG_1115p1:p.Glu1400Lys - Protein change
- E1400K, E1286K
- Other names
- -
- Canonical SPDI
- NC_000016.10:16154637:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00004
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
ABCC6 | - | - |
GRCh38 GRCh38 GRCh37 |
1441 | 1798 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (1) |
no assertion criteria provided
|
Mar 1, 2021 | RCV000499034.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 10, 2023 | RCV001857051.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(May 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002243025.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCC6 protein function. ClinVar contains an entry for this variant (Variation ID: 433353). This missense change has been observed in individual(s) with pseudoxanthoma elasticum (PMID: 15086542, 15459974, 23572048). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs63751241, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1400 of the ABCC6 protein (p.Glu1400Lys). (less)
|
|
Pathogenic
(Mar 01, 2021)
|
no assertion criteria provided
Method: research
|
Autosomal recessive inherited pseudoxanthoma elasticum
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
PXE International
Accession: SCV000589112.2
First in ClinVar: Oct 27, 2017 Last updated: Mar 07, 2021 |
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Angioid streaks (present)
Tissue: blood
Method: sanger sequencing
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Papule (present) , Angioid streaks (present)
Tissue: blood
Method: sanger sequencing
Observation 3:
Number of individuals with the variant: 1
Clinical Features:
Papule (present)
Tissue: blood
Method: sanger sequencing
Observation 4:
Number of individuals with the variant: 1
Clinical Features:
Papule (present) , Skin plaque (present) , Angioid streaks (present) , Weak or absent arterial pulse (present) , Angina pectoris (present) , Abnormal EKG (present)
Tissue: blood
Method: sanger sequencing
Observation 5:
Number of individuals with the variant: 1
Clinical Features:
Papule (present)
Tissue: blood
Method: sanger sequencing
Observation 6:
Number of individuals with the variant: 1
Clinical Features:
Angioid streaks (present)
Tissue: blood
Method: sanger sequencing
Observation 7:
Number of individuals with the variant: 1
Clinical Features:
Papule (present) , Skin plaque (present) , Angioid streaks (present) , Weak or absent arterial pulse (present)
Tissue: blood
Method: sanger sequencing
Observation 8:
Number of individuals with the variant: 1
Clinical Features:
Abnormally lax or hyperextensible skin (present) , Angioid streaks (present)
Tissue: blood
Method: sanger sequencing
Observation 9:
Number of individuals with the variant: 1
Clinical Features:
Papule (present) , Skin plaque (present) , Angioid streaks (present)
Tissue: blood
Method: sanger sequencing
Observation 10:
Number of individuals with the variant: 1
Clinical Features:
Papule (present)
Tissue: blood
Method: sanger sequencing
Observation 11:
Number of individuals with the variant: 1
Clinical Features:
Papule (present) , Skin plaque (present) , Angioid streaks (present)
Tissue: blood
Method: sanger sequencing
Observation 12:
Number of individuals with the variant: 1
Clinical Features:
Medial calcification of large arteries (present) , Intermittent claudication (present)
Tissue: blood
Method: sanger sequencing
Observation 13:
Number of individuals with the variant: 1
Tissue: blood
Comment on evidence:
No sign of PXE-related GASTRO, VASCULAR, or CARDIAC pathology observed
Method: sanger sequencing
Observation 14:
Number of individuals with the variant: 1
Clinical Features:
Stroke disorder (present) , Nephrolithiasis (present) , Papule (present) , Skin plaque (present) , Retinal hemorrhage (present) , Vascular surgery (present)
Tissue: blood
Method: sanger sequencing
Observation 15:
Number of individuals with the variant: 1
Clinical Features:
Stroke disorder (present) , Nephrolithiasis (present) , Papule (present) , Skin plaque (present) , Retinal hemorrhage (present) , Vascular surgery (present)
Tissue: blood
Method: sanger sequencing
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Reassessment of causality of ABCC6 missense variants associated with pseudoxanthoma elasticum based on Sherloc. | Verschuere S | Genetics in medicine : official journal of the American College of Medical Genetics | 2021 | PMID: 32873932 |
Clinical phenotypes and ABCC6 gene mutations in Brazilian families with pseudoxanthoma elasticum. | Faria CS | Acta dermato-venereologica | 2013 | PMID: 23572048 |
ABCC6 mutations in Italian families affected by pseudoxanthoma elasticum (PXE). | Gheduzzi D | Human mutation | 2004 | PMID: 15459974 |
Novel ABCC6 mutations in pseudoxanthoma elasticum. | Chassaing N | The Journal of investigative dermatology | 2004 | PMID: 15086542 |
Text-mined citations for rs63751241 ...
HelpRecord last updated Feb 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.