rs369866808
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000372292.8(SFTPD):c.883G>A(p.Ala295Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
ENST00000372292.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SFTPD | NM_003019.5 | c.883G>A | p.Ala295Thr | missense_variant | 8/8 | ENST00000372292.8 | NP_003010.4 | |
SFTPD | XM_011540087.2 | c.883G>A | p.Ala295Thr | missense_variant | 8/8 | XP_011538389.1 | ||
SFTPD | XM_011540088.3 | c.766G>A | p.Ala256Thr | missense_variant | 7/7 | XP_011538390.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SFTPD | ENST00000372292.8 | c.883G>A | p.Ala295Thr | missense_variant | 8/8 | 1 | NM_003019.5 | ENSP00000361366 | P1 | |
SFTPD | ENST00000678361.1 | n.3088G>A | non_coding_transcript_exon_variant | 4/4 | ||||||
SFTPD | ENST00000679234.1 | n.3009G>A | non_coding_transcript_exon_variant | 5/5 | ||||||
ENST00000421889.1 | n.234+1441C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152200Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251454Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135902
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461872Hom.: 0 Cov.: 33 AF XY: 0.0000316 AC XY: 23AN XY: 727230
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74478
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 11, 2017 | The p.Ala295Thr variant in SFTPD has not been previously reported in individuals with surfactant dysfunction, but has been identified in 2/30782 of South Asian chromosomes and 3/111682 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs369866808). Computational pr ediction tools and conservation analysis suggest that the p.Ala295Thr variant ma y not impact the protein, though this information is not predictive enough to ru le out pathogenicity. In summary, the clinical significance of the p.Ala295Thr v ariant is uncertain. ACMG/AMP Criteria applied: BP4 (Richards 2015). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at