chr19-8066137-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032447.5(FBN3):c.8212C>T(p.Arg2738Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,384 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2738H) has been classified as Uncertain significance.
Frequency
Consequence
NM_032447.5 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 | UniProt |
---|---|---|---|---|---|---|---|
FBN3 | NM_032447.5 | c.8212C>T | p.Arg2738Cys | missense_variant | 64/64 | ENST00000600128.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN3 | ENST00000600128.6 | c.8212C>T | p.Arg2738Cys | missense_variant | 64/64 | 1 | NM_032447.5 | ||
FBN3 | ENST00000270509.6 | c.8212C>T | p.Arg2738Cys | missense_variant | 63/63 | 1 | |||
FBN3 | ENST00000601739.5 | c.8212C>T | p.Arg2738Cys | missense_variant | 64/64 | 1 | |||
FBN3 | ENST00000651877.1 | c.8338C>T | p.Arg2780Cys | missense_variant | 64/64 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248606Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134874
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1461170Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726902
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with FBN3-related conditions. This variant is present in population databases (rs371800341, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2738 of the FBN3 protein (p.Arg2738Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at