chr19-8065992-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032447.5(FBN3):c.8357G>A(p.Gly2786Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,612,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2786S) has been classified as Uncertain significance.
Frequency
Consequence
NM_032447.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN3 | NM_032447.5 | c.8357G>A | p.Gly2786Asp | missense_variant | 64/64 | ENST00000600128.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN3 | ENST00000600128.6 | c.8357G>A | p.Gly2786Asp | missense_variant | 64/64 | 1 | NM_032447.5 | ||
FBN3 | ENST00000270509.6 | c.8357G>A | p.Gly2786Asp | missense_variant | 63/63 | 1 | |||
FBN3 | ENST00000601739.5 | c.8357G>A | p.Gly2786Asp | missense_variant | 64/64 | 1 | |||
FBN3 | ENST00000651877.1 | c.8483G>A | p.Gly2828Asp | missense_variant | 64/64 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152264Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247998Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134838
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1460570Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 726576
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152382Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74522
ClinVar
Submissions by phenotype
Flexion contracture Uncertain:1
Uncertain significance, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | - | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 20, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2786 of the FBN3 protein (p.Gly2786Asp). 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. 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 FBN3 protein function. ClinVar contains an entry for this variant (Variation ID: 816791). This missense change has been observed in individual(s) with joint contractures (PMID: 26752647). This variant is present in population databases (rs760179129, gnomAD 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at