rs1059058
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005411.5(SFTPA1):c.606C>T(p.Asp202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,610,506 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 44 hom., cov: 32)
Exomes 𝑓: 0.00079 ( 45 hom. )
Consequence
SFTPA1
NM_005411.5 synonymous
NM_005411.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0960
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=-0.82).
BP6
?
Variant 10-79613972-C-T is Benign according to our data. Variant chr10-79613972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.096 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2180/151926) while in subpopulation AFR AF= 0.0494 (2045/41392). AF 95% confidence interval is 0.0476. There are 44 homozygotes in gnomad4. There are 1009 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 44 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFTPA1 | NM_005411.5 | c.606C>T | p.Asp202= | synonymous_variant | 6/6 | ENST00000398636.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFTPA1 | ENST00000398636.8 | c.606C>T | p.Asp202= | synonymous_variant | 6/6 | 1 | NM_005411.5 | P1 | |
SFTPA1 | ENST00000419470.6 | c.651C>T | p.Asp217= | synonymous_variant | 6/6 | 1 | |||
SFTPA1 | ENST00000428376.6 | c.606C>T | p.Asp202= | synonymous_variant | 5/5 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0143 AC: 2173AN: 151810Hom.: 44 Cov.: 32
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GnomAD3 exomes AF: 0.00137 AC: 343AN: 250714Hom.: 16 AF XY: 0.00116 AC XY: 157AN XY: 135600
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GnomAD4 exome AF: 0.000788 AC: 1149AN: 1458580Hom.: 45 Cov.: 33 AF XY: 0.000761 AC XY: 552AN XY: 725832
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GnomAD4 genome ? AF: 0.0143 AC: 2180AN: 151926Hom.: 44 Cov.: 32 AF XY: 0.0136 AC XY: 1009AN XY: 74244
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ClinVar
Significance: Benign/Likely 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 | Asp217Asp 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 5.1% (9/176) of Yor uba (Nigerian) chromosomes from a broad population by the 1000 Genomes Project ( http://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs1059058). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at