14-91870237-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006329.4(FBLN5):āc.1334A>Cā(p.Gln445Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_006329.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBLN5 | NM_006329.4 | c.1334A>C | p.Gln445Pro | missense_variant | Exon 11 of 11 | ENST00000342058.9 | NP_006320.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727242
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1334A>C (p.Q445P) alteration is located in exon 11 (coding exon 11) of the FBLN5 gene. This alteration results from a A to C substitution at nucleotide position 1334, causing the glutamine (Q) at amino acid position 445 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 445 of the FBLN5 protein (p.Gln445Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FBLN5-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at