ClinVar Genomic variation as it relates to human health
NM_000033.4(ABCD1):c.1679C>T (p.Pro560Leu)
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.
Pathogenic(9); Benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000033.4(ABCD1):c.1679C>T (p.Pro560Leu)
Variation ID: 92320 Accession: VCV000092320.24
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq28 X: 153740618 (GRCh38) [ NCBI UCSC ] X: 153006072 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Dec 26, 2017 Feb 28, 2024 Oct 29, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000033.4:c.1679C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000024.2:p.Pro560Leu missense NC_000023.11:g.153740618C>T NC_000023.10:g.153006072C>T NG_009022.2:g.20751C>T LRG_1017:g.20751C>T LRG_1017t1:c.1679C>T LRG_1017p1:p.Pro560Leu P33897:p.Pro560Leu - Protein change
- P560L
- Other names
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- Canonical SPDI
- NC_000023.11:153740617:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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ABCD1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1495 | 1734 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Oct 29, 2023 | RCV000077958.24 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Aug 8, 2022 | RCV000723625.19 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 10, 2017 | RCV002399466.8 | |
Benign (1) |
criteria provided, single submitter
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May 12, 2023 | RCV003483467.1 |
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. |
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Pathogenic
(Nov 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002045837.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
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Pathogenic
(May 13, 2022)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002547816.1
First in ClinVar: Jul 17, 2022 Last updated: Jul 17, 2022 |
Comment:
Variant summary: ABCD1 c.1679C>T (p.Pro560Leu) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain of the encoded protein sequence. Five … (more)
Variant summary: ABCD1 c.1679C>T (p.Pro560Leu) results in a non-conservative amino acid change located in the ABC transporter-like, ATP-binding domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183088 control chromosomes. c.1679C>T has been reported in the literature in many individuals affected with Adrenoleukodystrophy (example Braun_1995, Feigenbaum_1996, Takano_1999, Kemp_2001, Jack_2013, Capalbo_2021). These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 10, 2017)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002710978.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.P560L pathogenic mutation (also known as c.1679C>T), located in coding exon 7 of the ABCD1 gene, results from a C to T substitution at … (more)
The p.P560L pathogenic mutation (also known as c.1679C>T), located in coding exon 7 of the ABCD1 gene, results from a C to T substitution at nucleotide position 1679. The proline at codon 560 is replaced by leucine, an amino acid with similar properties. This mutation has been reported in multiple affected males with the childhood cerebral form of X-linked adrenoleukodystrophy and adrenomyeloneuropathy (AMN) (Braun A et al. Am. J. Hum. Genet., 1995 Apr;56:854-61; Feigenbaum V et al. Am. J. Hum. Genet., 1996 Jun;58:1135-44; Shukla P et al. Clin. Chim. Acta, 2011 Nov;412:2289-95; Wang Y et al. Mol. Genet. Metab. Jun;104:160-6; Park HJ et al. Yonsei Med. J., 2014 May;55:676-82; Jack GH et al. Case Rep Neurol Med, 2013 Jun;2013:491790). In addition, adrenoleukodystrophy protein (ALDP) analysis in cells from affected individuals demonstrated a reduced level or absent protein compared to wild type (Feigenbaum V et al. Am. J. Hum. Genet., 1996 Jun;58:1135-44). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(Dec 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV003835955.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
(X-linked inheritance)
Affected status: yes
Allele origin:
maternal
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Intergen, Intergen Genetics and Rare Diseases Diagnosis Center
Accession: SCV004024557.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
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Benign
(May 12, 2023)
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criteria provided, single submitter
Method: research
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004231795.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
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Pathogenic
(Aug 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022833.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Oct 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Adrenoleukodystrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000629992.5
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 560 of the ABCD1 protein (p.Pro560Leu). … (more)
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 560 of the ABCD1 protein (p.Pro560Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with X-linked adrenoleukodystrophy (PMID: 7717396, 8651290, 20661612, 21700483, 23566833, 24719134). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 92320). 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) performed at Invitae indicates that this missense variant is expected to disrupt ABCD1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 30, 2013)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000109787.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(May 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001783337.3
First in ClinVar: Aug 14, 2021 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34997422, 34649108, 10190819, 21889498, 21068741, 20661612, 8651290, 24719134, 11748843, 20800589, 21300044, 22479560, 23864971, 22189598, 12530690, 23566833, 21700483, 7717396) (less)
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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 |
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Primary Adrenal Insufficiency in Childhood: Data From a Large Nationwide Cohort. | Capalbo D | The Journal of clinical endocrinology and metabolism | 2021 | PMID: 33247909 |
Clinical and genetic aspects in twelve Korean patients with adrenomyeloneuropathy. | Park HJ | Yonsei medical journal | 2014 | PMID: 24719134 |
Clinical manifest x-linked recessive adrenoleukodystrophy in a female. | Jack GH | Case reports in neurological medicine | 2013 | PMID: 23864971 |
ABCD1 mutations and phenotype distribution in Chinese patients with X-linked adrenoleukodystrophy. | Niu YF | Gene | 2013 | PMID: 23566833 |
Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy. | Pereira Fdos S | PloS one | 2012 | PMID: 22479560 |
A mixture of oleic, erucic and conjugated linoleic acids modulates cerebrospinal fluid inflammatory markers and improve somatosensorial evoked potential in X-linked adrenoleukodystrophy female carriers. | Cappa M | Journal of inherited metabolic disease | 2012 | PMID: 22189598 |
Molecular analysis of ABCD1 gene in Indian patients with X-linked adrenoleukodystrophy. | Shukla P | Clinica chimica acta; international journal of clinical chemistry | 2011 | PMID: 21889498 |
X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism. | Wang Y | Molecular genetics and metabolism | 2011 | PMID: 21700483 |
Molecular diagnosis of X-linked adrenoleukodystrophy: experience from a clinical genetic laboratory in mainland China with report of 13 novel mutations. | Lan F | Clinica chimica acta; international journal of clinical chemistry | 2011 | PMID: 21300044 |
X-linked adrenoleukodystrophy: diagnostic and follow-up system in Japan. | Shimozawa N | Journal of human genetics | 2011 | PMID: 21068741 |
Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes. | Matsukawa T | Neurogenetics | 2011 | PMID: 20661612 |
A rapid and sensitive protocol for prenatal molecular diagnosis of X-linked adrenoleukodystrophy. | Lan F | Clinica chimica acta; international journal of clinical chemistry | 2010 | PMID: 20800589 |
Symptoms in carriers of adrenoleukodystrophy relate to skewed X inactivation. | Maier EM | Annals of neurology | 2002 | PMID: 12402273 |
ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. | Kemp S | Human mutation | 2001 | PMID: 11748843 |
Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese patients with X-linked adrenoleukodystrophy. | Takano H | Archives of neurology | 1999 | PMID: 10190819 |
Mutational and protein analysis of patients and heterozygous women with X-linked adrenoleukodystrophy. | Feigenbaum V | American journal of human genetics | 1996 | PMID: 8651290 |
Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes. | Braun A | American journal of human genetics | 1995 | PMID: 7717396 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ABCD1 | - | - | - | - |
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Text-mined citations for rs398123105 ...
HelpRecord last updated Apr 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.