14-91877585-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_006329.4(FBLN5):c.1087G>A(p.Ala363Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,868 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006329.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBLN5 | NM_006329.4 | c.1087G>A | p.Ala363Thr | missense_variant | Exon 10 of 11 | ENST00000342058.9 | NP_006320.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251450Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135896
GnomAD4 exome AF: 0.0000568 AC: 83AN: 1461696Hom.: 0 Cov.: 32 AF XY: 0.0000564 AC XY: 41AN XY: 727168
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74338
ClinVar
Submissions by phenotype
Macular degeneration, age-related, 3 Pathogenic:2
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not provided Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 363 of the FBLN5 protein (p.Ala363Thr). This variant is present in population databases (rs121434302, gnomAD 0.005%). This missense change has been observed in individual(s) with age-related macular degeneration (PMID: 15269314). ClinVar contains an entry for this variant (Variation ID: 5482). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FBLN5 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Age-related macular degeneration Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at