rs121918560
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP5
The NM_001317778.2(SFTPC):c.563T>C(p.Leu188Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L188Q) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 35)
Consequence
SFTPC
NM_001317778.2 missense
NM_001317778.2 missense
Scores
4
10
4
Clinical Significance
Conservation
PhyloP100: 1.41
Genes affected
SFTPC (HGNC:10802): (surfactant protein C) This gene encodes the pulmonary-associated surfactant protein C (SPC), an extremely hydrophobic surfactant protein essential for lung function and homeostasis after birth. Pulmonary surfactant is a surface-active lipoprotein complex composed of 90% lipids and 10% proteins which include plasma proteins and apolipoproteins SPA, SPB, SPC and SPD. The surfactant is secreted by the alveolar cells of the lung and maintains the stability of pulmonary tissue by reducing the surface tension of fluids that coat the lung. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 2, also called pulmonary alveolar proteinosis due to surfactant protein C deficiency, and are associated with interstitial lung disease in older infants, children, and adults. Alternatively spliced transcript variants encoding different protein isoforms have been identified.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a propeptide (size 138) in uniprot entity PSPC_HUMAN there are 19 pathogenic changes around while only 2 benign (90%) in NM_001317778.2
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.
PP5
Variant 8-22164028-T-C is Pathogenic according to our data. Variant chr8-22164028-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 13214.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-22164028-T-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SFTPC | NM_001317778.2 | c.563T>C | p.Leu188Pro | missense_variant | 5/6 | ENST00000679463.1 | NP_001304707.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SFTPC | ENST00000679463.1 | c.563T>C | p.Leu188Pro | missense_variant | 5/6 | NM_001317778.2 | ENSP00000505152 | A1 |
Frequencies
GnomAD3 genomes Cov.: 35
GnomAD3 genomes
Cov.:
35
GnomAD4 exome Cov.: 52
GnomAD4 exome
Cov.:
52
GnomAD4 genome Cov.: 35
GnomAD4 genome
Cov.:
35
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Surfactant metabolism dysfunction, pulmonary, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2009 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
A;A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Vest4
MutPred
Loss of sheet (P = 0.0037);.;.;
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at