NM_001089.3(ABCA3):c.4085C>T (p.Ala1362Val) AND Surfactant metabolism dysfunction, pulmonary, 3

Clinical significance:Conflicting interpretations of pathogenicity, Benign(1);Uncertain significance(1) (Last evaluated: May 20, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000856676.2

Allele description [Variation Report for NM_001089.3(ABCA3):c.4085C>T (p.Ala1362Val)]

NM_001089.3(ABCA3):c.4085C>T (p.Ala1362Val)

Gene:
ABCA3:ATP binding cassette subfamily A member 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_001089.3(ABCA3):c.4085C>T (p.Ala1362Val)
HGVS:
  • NC_000016.10:g.2281460G>A
  • NG_011790.1:g.64287C>T
  • NM_001089.3:c.4085C>TMANE SELECT
  • NP_001080.2:p.Ala1362Val
  • NC_000016.9:g.2331461G>A
  • NM_001089.2:c.4085C>T
Protein change:
A1362V
Links:
dbSNP: rs145251229
NCBI 1000 Genomes Browser:
rs145251229
Molecular consequence:
  • NM_001089.3:c.4085C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Surfactant metabolism dysfunction, pulmonary, 3 (SMDP3)
Synonyms:
INTERSTITIAL LUNG DISEASE DUE TO ABCA3 DEFICIENCY; PULMONARY ALVEOLAR PROTEINOSIS, CONGENITAL, 3
Identifiers:
MONDO: MONDO:0012582; MedGen: C1970456; OMIM: 610921

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000999222Johns Hopkins Genomics, Johns Hopkins Universitycriteria provided, single submitter
Uncertain significance
(May 20, 2019)
germlineclinical testing

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

SCV001278810Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Benign
(Apr 27, 2017)
germlineclinical testing

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

Citation Link

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

Hereditary interstitial lung diseases manifesting in early childhood in Japan.

Akimoto T, Cho K, Hayasaka I, Morioka K, Kaneshi Y, Furuta I, Yamada M, Ariga T, Minakami H.

Pediatr Res. 2014 Nov;76(5):453-8. doi: 10.1038/pr.2014.114. Epub 2014 Aug 8.

PubMed [citation]
PMID:
25105258

Details of each submission

From Johns Hopkins Genomics, Johns Hopkins University, SCV000999222.1

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

Description

This previously reported ABCA3 variant (rs145251229) has been identified in large population datasets and the minor allele frequency is neither low enough to consider the variant rare (<0.1%) nor high enough to consider it a population polymorphism (>1%) within a subpopulation (gnomAD total: 72/282632 alleles; 0.02547%, no homozygotes). Two bioinformatic tools queried predict that this substitution would be tolerated, and the alanine residue at this position is not evolutionarily conserved across species assessed. Bioinformatic analysis predicts that this missense variant would not affect normal exon 27 splicing, although this has not been confirmed experimentally to our knowledge. Due to insufficient evidence that this variant is deleterious, the clinical significance of c.4085C>T is uncertain at this time.

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

From Illumina Clinical Services Laboratory,Illumina, SCV001278810.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

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

Last Updated: Feb 27, 2021

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