14-91870240-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006329.4(FBLN5):c.1331C>T(p.Ser444Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
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.1331C>T | p.Ser444Leu | missense_variant | Exon 11 of 11 | ENST00000342058.9 | NP_006320.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251430Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135886
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461854Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727230
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
not provided Uncertain:2
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This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 444 of the FBLN5 protein (p.Ser444Leu). This variant is present in population databases (rs749952010, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with FBLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 870929). 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 expected to disrupt FBLN5 protein function with a positive 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. -
Inborn genetic diseases Uncertain:1
The c.1331C>T (p.S444L) alteration is located in exon 11 (coding exon 11) of the FBLN5 gene. This alteration results from a C to T substitution at nucleotide position 1331, causing the serine (S) at amino acid position 444 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at