Submissions for variant NM_001089.3(ABCA3):c.4214C>T (p.Ala1405Val)

gnomAD frequency: 0.00010  dbSNP: rs149559041

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Johns Hopkins Genomics, Johns Hopkins University	RCV000787034	SCV000925946	uncertain significance	Interstitial lung disease due to ABCA3 deficiency	2019-03-11	criteria provided, single submitter	clinical testing	This ABCA3 variant (rs149559041) is rare in large population datasets (gnomAD: 15/282448 total alleles; 0.005%; no homozygotes). ABCA3 c.4214C>T has not been reported in ClinVar nor the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be tolerated, and the alanine residue at this position is highly evolutionarily conserved across most species assessed. Bioinformatic analysis predicts that this variant would not affect normal exon 28 splicing, although this has not been confirmed experimentally to our knowledge. The clinical significance of c.4214C>T is uncertain at this time.
Ambry Genetics	RCV002332575	SCV002630083	uncertain significance	Hereditary pulmonary alveolar proteinosis	2022-05-27	criteria provided, single submitter	clinical testing	The p.A1405V variant (also known as c.4214C>T), located in coding exon 25 of the ABCA3 gene, results from a C to T substitution at nucleotide position 4214. The alanine at codon 1405 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.