Submissions for variant NM_001317778.2(SFTPC):c.157G>A (p.Ala53Thr)

gnomAD frequency: 0.00011  dbSNP: rs200039720

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001163545	SCV001325597	benign	Surfactant metabolism dysfunction, pulmonary, 2	2017-04-28	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001163546	SCV001325598	benign	Interstitial lung disease 2	2017-04-28	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Johns Hopkins Genomics, Johns Hopkins University	RCV001163545	SCV001425402	uncertain significance	Surfactant metabolism dysfunction, pulmonary, 2	2020-04-10	criteria provided, single submitter	clinical testing	This variant has been previously reported in individuals with pulmonary disease of varying severity. SFTPC c.157G>A (rs200039720) is present in a large population dataset (gnomAD: 43/280968 total alleles; 0.015%; no homozygotes). This variant has not been reported in ClinVar, to our knowledge. Studies show that individuals carrying this variant have no difference in lung function as compared to non-carriers, however, the effect of this variant on pulmonary-associated surfactant protein C function has not been experimentally assessed to our knowledge. Three bioinformatic tools queried predict that the substitution would be damaging, but these algorithms have low specificity, especially for predicting gain of function or dominant negative variants. Due to insufficient evidence, we consider the clinical significance of c.157G>A to be uncertain at this time.
GeneDx	RCV001797157	SCV002038865	uncertain significance	not provided	2023-03-27	criteria provided, single submitter	clinical testing	Reported in several children with infantile-onset lung disease who were also reported to have another SFTPC variant (p.(L181V)) on the same allele (in cis), but the variant was inherited from an unaffected parent (Willander et al., 2012; Kroner et al., 2015); A study evaluating large population-based cohorts for the p.(A53T) variant found that p.(A53T) was associated with a two-fold increased risk of asthma, but there was no significant association with the risk of chronic obstructive pulmonary disease or interstitial lung disease (Baekvad-Hansen et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30487145, 22308375, 19910179, 25657025)