Submissions for variant NM_001089.3(ABCA3):c.3613G>A (p.Gly1205Arg)

gnomAD frequency: 0.00011  dbSNP: rs549977217

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001115431	SCV001273408	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001317105	SCV001507752	likely benign	not provided	2024-03-18	criteria provided, single submitter	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV001824065	SCV002072634	uncertain significance	Disorder of lung		criteria provided, single submitter	clinical testing	The p.Gly1205Arg substitutes the glycine at position 1205 with arginine. The majority of in silico tools predict that this variant is tolerated and this position is not conserved across species. This missense variant has been documented in a large database of presumably healthy individuals, with an allele frequency of 0.6% in individuals with East Asian ancestry (113 out of 18,388 alleles, ~ 1/81 are carriers, Genome Aggregation Database).
Fulgent Genetics, Fulgent Genetics	RCV001115431	SCV002786579	uncertain significance	Interstitial lung disease due to ABCA3 deficiency	2022-03-04	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV001115431	SCV004024528	uncertain significance	Interstitial lung disease due to ABCA3 deficiency	2023-05-24	criteria provided, single submitter	clinical testing	This ABCA3 missense variant has been reported in the compound heterozygous state in an infant with unexplained respiratory distress who later recovered. This variant has also been identified in the heterozygous state in two patients with sporadic idiopathic pulmonary fibrosis, and case-control analysis showed higher allele frequency in the cohort of patients with connective tissue disease-associated interstitial lung disease compared with controls. c.3613G>A in ABCA3 (rs549977217) is present in a large population dataset (gnomAD v2.1.1: 121/282218 total alleles; 0.043%; no homozygotes), and has been reported in ClinVar (Variation ID 884386). Two bioinformatic tools queried predict that this substitution would be tolerated, and the glycine residue at this position is evolutionarily conserved across some of the species assessed. We consider the clinical significance of c.3613G>A in ABCA3 to be uncertain.