NM_000033.4(ABCD1):c.521A>C (p.Tyr174Ser) AND Adrenoleukodystrophy

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jan 19, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000850177.3

Allele description [Variation Report for NM_000033.4(ABCD1):c.521A>C (p.Tyr174Ser)]

NM_000033.4(ABCD1):c.521A>C (p.Tyr174Ser)

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.521A>C (p.Tyr174Ser)
HGVS:
  • NC_000023.11:g.153725787A>C
  • NG_009022.2:g.5920A>C
  • NG_023231.1:g.3960T>G
  • NM_000033.4:c.521A>CMANE SELECT
  • NP_000024.2:p.Tyr174Ser
  • LRG_1017t1:c.521A>C
  • LRG_1017:g.5920A>C
  • LRG_1017p1:p.Tyr174Ser
  • NC_000023.10:g.152991242A>C
  • NM_000033.3:c.521A>C
Protein change:
Y174S
Links:
dbSNP: rs1557052390
NCBI 1000 Genomes Browser:
rs1557052390
Molecular consequence:
  • NM_000033.4:c.521A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Adrenoleukodystrophy (ALD)
Synonyms:
ADDISON DISEASE AND CEREBRAL SCLEROSIS; BRONZE SCHILDER DISEASE; MELANODERMIC LEUKODYSTROPHY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018544; MedGen: C0162309; OMIM: 300100

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
SCV000992372Johns Hopkins Genomics, Johns Hopkins Universitycriteria provided, single submitter
Likely pathogenic
(Jun 4, 2019)
germlineclinical testing

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

SCV001220972Invitaecriteria provided, single submitter
Pathogenic
(Jan 19, 2020)
germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

De novo missense mutation Y174S in exon 1 of the adrenoleukodystrophy (ALD) gene.

Barceló A, Girós M, Sarde CO, Pintos G, Mandel JL, Pàmpols T, Estivill X.

Hum Genet. 1995 Feb;95(2):235-7.

PubMed [citation]
PMID:
7860075
See all PubMed Citations (9)

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV000992372.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001220972.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

This sequence change replaces tyrosine with serine at codon 174 of the ABCD1 protein (p.Tyr174Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with X-linked adrenoleukodystrophy (PMID: 7860075, 15811009, 21907609, 28456143). In at least one individual the data is consistent with the variant being de novo. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Tyr174 amino acid residue in ABCD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10737980, 24722136, 15800013, 15811009). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 10, 2021

Support Center