Submissions for variant NM_001089.3(ABCA3):c.1465A>T (p.Met489Leu)

dbSNP: rs150543946

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001007603	SCV000396051	uncertain significance	Interstitial lung disease due to ABCA3 deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Johns Hopkins Genomics, Johns Hopkins University	RCV001007603	SCV001167286	likely benign	Interstitial lung disease due to ABCA3 deficiency	2019-09-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002392863	SCV002698794	uncertain significance	Hereditary pulmonary alveolar proteinosis	2017-06-19	criteria provided, single submitter	clinical testing	The p.M489L variant (also known as c.1465A>T), located in coding exon 9 of the ABCA3 gene, results from an A to T substitution at nucleotide position 1465. The methionine at codon 489 is replaced by leucine, an amino acid with highly similar properties. This variant was identified in one non-smoker with a low FEV1%; however, no further study or inquiry was performed for this variant (Bækvad-Hansen M et al. Respir. Res., 2012 Aug;13:67). This amino acid position is poorly 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.
CeGaT Center for Human Genetics Tuebingen	RCV003417996	SCV004142950	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	ABCA3: BP4