Submissions for variant NM_001089.3(ABCA3):c.160G>A (p.Ala54Thr)

gnomAD frequency: 0.00075  dbSNP: rs147278907

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000288211	SCV000396162	uncertain significance	Interstitial lung disease due to ABCA3 deficiency	2018-01-12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000894058	SCV001038023	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000894058	SCV002006934	uncertain significance	not provided	2020-03-26	criteria provided, single submitter	clinical testing	Identified in a patient with ABCA3 deficiency who also harbored a second variant in the ABCA3 gene (phase unknown) in published literature (Wambach et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24871971)
Ambry Genetics	RCV002392865	SCV002703124	uncertain significance	Hereditary pulmonary alveolar proteinosis	2019-01-02	criteria provided, single submitter	clinical testing	The p.A54T variant (also known as c.160G>A), located in coding exon 2 of the ABCA3 gene, results from a G to A substitution at nucleotide position 160. The alanine at codon 54 is replaced by threonine, an amino acid with similar properties. In one study, this variant was reported in one individual in conjunction with two additional alterations (Wambach JA et al. Am. J. Respir. Crit. Care Med., 2014 Jun;189:1538-43). 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.
PreventionGenetics, part of Exact Sciences	RCV003957647	SCV004774740	likely benign	ABCA3-related disorder	2020-08-07	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).