chr19-8066097-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032447.5(FBN3):c.8252G>A(p.Arg2751His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R2751P) 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.8252G>A | p.Arg2751His | missense_variant | 64/64 | ENST00000600128.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN3 | ENST00000600128.6 | c.8252G>A | p.Arg2751His | missense_variant | 64/64 | 1 | NM_032447.5 | ||
FBN3 | ENST00000270509.6 | c.8252G>A | p.Arg2751His | missense_variant | 63/63 | 1 | |||
FBN3 | ENST00000601739.5 | c.8252G>A | p.Arg2751His | missense_variant | 64/64 | 1 | |||
FBN3 | ENST00000651877.1 | c.8378G>A | p.Arg2793His | missense_variant | 64/64 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250056Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135340
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461166Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726904
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2023 | The c.8252G>A (p.R2751H) alteration is located in exon 63 (coding exon 63) of the FBN3 gene. This alteration results from a G to A substitution at nucleotide position 8252, causing the arginine (R) at amino acid position 2751 to be replaced by a histidine (H). 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