NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 31, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000727694.5

Allele description [Variation Report for NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu)]

NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu)

Gene:
ABCD1:ATP binding cassette subfamily D member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000033.4(ABCD1):c.1628C>T (p.Pro543Leu)
HGVS:
  • NC_000023.11:g.153740231C>T
  • NG_009022.2:g.20364C>T
  • NM_000033.4:c.1628C>TMANE SELECT
  • NP_000024.2:p.Pro543Leu
  • LRG_1017t1:c.1628C>T
  • LRG_1017:g.20364C>T
  • LRG_1017p1:p.Pro543Leu
  • NC_000023.10:g.153005685C>T
  • NM_000033.3:c.1628C>T
Protein change:
P543L
Links:
dbSNP: rs1557054776
NCBI 1000 Genomes Browser:
rs1557054776
Molecular consequence:
  • NM_000033.4:c.1628C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000855037EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(May 25, 2018)
germlineclinical testing

Citation Link,

SCV000883320ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Pathogenic
(May 16, 2018)
germlineclinical testing

Citation Link,

SCV001475502Athena Diagnostics Inccriteria provided, single submitter
Likely pathogenic
(Mar 31, 2020)
unknownclinical testing

PubMed (11)
[See all records that cite these PMIDs]

SCV002022866PerkinElmer Genomicsno assertion criteria providedPathogenic
(Sep 28, 2021)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: clinical, laboratory and genetic findings.

Korenke GC, Roth C, Krasemann E, H├╝fner M, Hunneman DH, Hanefeld F.

Eur J Endocrinol. 1997 Jul;137(1):40-7.

PubMed [citation]
PMID:
9242200

Pathogenicity of novel ABCD1 variants: The need for biochemical testing in the era of advanced genetics.

Schackmann MJ, Ofman R, van Geel BM, Dijkstra IM, van Engelen K, Wanders RJ, Engelen M, Kemp S.

Mol Genet Metab. 2016 Jun;118(2):123-7. doi: 10.1016/j.ymgme.2016.03.009. Epub 2016 Apr 3.

PubMed [citation]
PMID:
27067449
See all PubMed Citations (11)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000855037.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000883320.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The ABCD1 c.1628C>T; p.Pro543Leu variant has been described in several individuals affected with adrenoleukodystrophy (ALD) with no detectable level of peroxisomal ABC half-transporter (ALDP) in their cells (see link to ALD ABCD1 database and references therein). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The proline at codon 543 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. Another variant at this codon (c.1627C>T; p.Pro543Ser) has been identified in patients with ALD and is considered pathogenic (see link to ALD ABCD1 database and references therein). Based on available information, the p.Pro543Leu variant is considered pathogenic. References: ALD ABCD1 Database: http://adrenoleukodystrophy.info/mutations-and-variants-in-abcd1

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Athena Diagnostics Inc, SCV001475502.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

Not found in the total gnomAD dataset, and the data is high quality. Predicted to have a damaging effect on the protein. Found in multiple individuals with expected phenotype for this gene.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From PerkinElmer Genomics, SCV002022866.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 28, 2021

Support Center