rs1059057
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005411.5(SFTPA1):āc.399A>Gā(p.Thr133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 1,613,874 control chromosomes in the GnomAD database, including 6,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.066 ( 552 hom., cov: 32)
Exomes š: 0.077 ( 5723 hom. )
Consequence
SFTPA1
NM_005411.5 synonymous
NM_005411.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.33
Genes affected
SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BP6
?
Variant 10-79613765-A-G is Benign according to our data. Variant chr10-79613765-A-G is described in ClinVar as [Benign]. Clinvar id is 165199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.33 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFTPA1 | NM_005411.5 | c.399A>G | p.Thr133= | synonymous_variant | 6/6 | ENST00000398636.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFTPA1 | ENST00000398636.8 | c.399A>G | p.Thr133= | synonymous_variant | 6/6 | 1 | NM_005411.5 | P1 | |
SFTPA1 | ENST00000419470.6 | c.444A>G | p.Thr148= | synonymous_variant | 6/6 | 1 | |||
SFTPA1 | ENST00000428376.6 | c.399A>G | p.Thr133= | synonymous_variant | 5/5 | 1 | P1 | ||
SFTPA1 | ENST00000429958.5 | c.399A>G | p.Thr133= | synonymous_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0662 AC: 10071AN: 152128Hom.: 545 Cov.: 32
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GnomAD3 exomes AF: 0.0988 AC: 24723AN: 250160Hom.: 2024 AF XY: 0.0995 AC XY: 13472AN XY: 135440
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GnomAD4 exome AF: 0.0768 AC: 112221AN: 1461628Hom.: 5723 Cov.: 32 AF XY: 0.0796 AC XY: 57904AN XY: 727116
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GnomAD4 genome ? AF: 0.0663 AC: 10090AN: 152246Hom.: 552 Cov.: 32 AF XY: 0.0698 AC XY: 5197AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Thr148Thr in exon 6 of SFTPA1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 6.7% (572/8586) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs141764116). - |
SFTPA1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 27, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at