Submissions for variant NM_001317778.2(SFTPC):c.*12T>A

gnomAD frequency: 0.00027  dbSNP: rs200469074

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000288374	SCV000473033	benign	Surfactant metabolism dysfunction, pulmonary, 2	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000329388	SCV000473034	benign	Interstitial lung disease 2	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000430447	SCV000516945	likely benign	not specified	2015-05-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV002446618	SCV002735403	uncertain significance	Hereditary pulmonary alveolar proteinosis	2015-05-27	criteria provided, single submitter	clinical testing	The c.*12T>A variant is located in the 3' untranslated region (3’ UTR) of the SFTPC gene. This variant results from a T to A substitution the last translated codon. This variant was previously reported in the SNPDatabase as rs200469074. Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0% (0/2098) total alleles studied. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/12290) total alleles studied, having been observed in 0.05% (2/3988) African American alleles. This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of c.*12T>A remains unclear.