ClinVar Miner

Submissions for variant NM_001089.3(ABCA3):c.371A>G (p.Asn124Ser)

gnomAD frequency: 0.00084  dbSNP: rs142977595
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000612210 SCV000711276 likely benign not specified 2019-01-22 criteria provided, single submitter clinical testing The p.Asn124Ser variant in ABCA3 is classified as likely benign because it has has been identified in 0.16% (209/128312) of European and 0.13% (32/23120) of Finnish chromosomes including 1 homozygote by gnomAD (http://gnomad.broadinstitute.org), and because computational prediction tools and conservation analysis suggest that the variant may not impact the protein. ACMG/AMP criteria applied: BS1_Supporting, BP4.
Illumina Laboratory Services, Illumina RCV001121934 SCV001280596 uncertain significance Interstitial lung disease due to ABCA3 deficiency 2017-04-27 criteria provided, single submitter clinical testing 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV002065192 SCV002476283 likely benign not provided 2024-01-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV002350435 SCV002623125 uncertain significance Hereditary pulmonary alveolar proteinosis 2018-02-26 criteria provided, single submitter clinical testing The p.N124S variant (also known as c.371A>G), located in coding exon 3 of the ABCA3 gene, results from an A to G substitution at nucleotide position 371. The asparagine at codon 124 is replaced by serine, an amino acid with highly similar properties. A study of the N-linked glycosylation site at residue 124 found that single mutations at the glycosylation site fail to disrupt the trafficking pattern of ABCA3 to cytosolic lysosomal-related organelles or alter their function as lipid transporters (Beers MF et al. Am. J. Physiol. Lung Cell Mol. Physiol., 2013 Dec;305:L970-80). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear.

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