NM_001089.3(ABCA3):c.4090G>A (p.Glu1364Lys) AND Interstitial lung disease due to ABCA3 deficiency

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 8, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004579628.2

Allele description [Variation Report for NM_001089.3(ABCA3):c.4090G>A (p.Glu1364Lys)]

NM_001089.3(ABCA3):c.4090G>A (p.Glu1364Lys)

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.4090G>A (p.Glu1364Lys)

HGVS:

NC_000016.10:g.2281455C>T
NG_011790.1:g.64292G>A
NG_011790.2:g.64273G>A
NM_001089.3:c.4090G>AMANE SELECT
NP_001080.2:p.Glu1364Lys
NC_000016.9:g.2331456C>T

Protein change:

E1364K

Molecular consequence:

NM_001089.3:c.4090G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Interstitial lung disease due to ABCA3 deficiency
Synonyms:: PULMONARY ALVEOLAR PROTEINOSIS, CONGENITAL, 3; Surfactant metabolism dysfunction, pulmonary, 3
Identifiers:: MONDO: MONDO:0012582; MedGen: C1970456; OMIM: 610921

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005062099	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Mar 8, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27516224, 24871971, 36808083, 37108718 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005062099

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Mar 8, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Lung disease caused by ABCA3 mutations.

Kröner C, Wittmann T, Reu S, Teusch V, Klemme M, Rauch D, Hengst M, Kappler M, Cobanoglu N, Sismanlar T, Aslan AT, Campo I, Proesmans M, Schaible T, Terheggen-Lagro S, Regamey N, Eber E, Seidenberg J, Schwerk N, Aslanidis C, Lohse P, Brasch F, et al.

Thorax. 2017 Mar;72(3):213-220. doi: 10.1136/thoraxjnl-2016-208649. Epub 2016 Aug 11.

PubMed [citation]

PMID:: 27516224

Genotype-phenotype correlations for infants and children with ABCA3 deficiency.

Wambach JA, Casey AM, Fishman MP, Wegner DJ, Wert SE, Cole FS, Hamvas A, Nogee LM.

Am J Respir Crit Care Med. 2014 Jun 15;189(12):1538-43. doi: 10.1164/rccm.201402-0342OC.

PubMed [citation]

PMID:: 24871971
PMCID:: PMC4226019

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005062099.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: ABCA3 c.4090G>A (p.Glu1364Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251214 control chromosomes. c.4090G>A has been reported in the literature as biallelic homozygous or compound heterozygous genotypes in individuals affected with Pulmonary surfactant metabolism dysfunction (example, Wambach_2014, Kroner_2017, Li_2023). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Yang_2023). The most pronounced variant effect results in impairment of intracellular trafficking and pumping activity across different assays evaluated. The following publications have been ascertained in the context of this evaluation (PMID: 27516224, 36808083, 24871971, 37108718). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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