rs1553380888
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_000542.5(SFTPB):c.465G>T(p.Gly155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
SFTPB
NM_000542.5 synonymous
NM_000542.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0360
Genes affected
SFTPB (HGNC:10801): (surfactant protein B) This gene encodes the pulmonary-associated surfactant protein B (SPB), an amphipathic 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. The SPB enhances the rate of spreading and increases the stability of surfactant monolayers in vitro. Multiple mutations in this gene have been identified, which cause pulmonary surfactant metabolism dysfunction type 1, also called pulmonary alveolar proteinosis due to surfactant protein B deficiency, and are associated with fatal respiratory distress in the neonatal period. Alternatively spliced transcript variants encoding the same protein have been identified.[provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 2-85665723-C-A is Pathogenic according to our data. Variant chr2-85665723-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 13205.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFTPB | NM_000542.5 | c.465G>T | p.Gly155= | synonymous_variant | 5/11 | ENST00000519937.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFTPB | ENST00000519937.7 | c.465G>T | p.Gly155= | synonymous_variant | 5/11 | 1 | NM_000542.5 | P1 | |
SFTPB | ENST00000393822.7 | c.465G>T | p.Gly155= | synonymous_variant | 6/12 | 1 | P1 | ||
SFTPB | ENST00000409383.6 | c.465G>T | p.Gly155= | synonymous_variant | 6/12 | 1 | P1 | ||
SFTPB | ENST00000428225.5 | c.456G>T | p.Gly152= | synonymous_variant | 5/11 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727240
GnomAD4 exome
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5
AN:
1461882
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32
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3
AN XY:
727240
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Surfactant metabolism dysfunction, pulmonary, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2000 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at