19-8066127-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032447.5(FBN3):c.8222T>C(p.Ile2741Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I2741I) has been classified as Likely benign.
Frequency
Consequence
NM_032447.5 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN3 | NM_032447.5 | c.8222T>C | p.Ile2741Thr | missense_variant | 64/64 | ENST00000600128.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN3 | ENST00000600128.6 | c.8222T>C | p.Ile2741Thr | missense_variant | 64/64 | 1 | NM_032447.5 | ||
FBN3 | ENST00000270509.6 | c.8222T>C | p.Ile2741Thr | missense_variant | 63/63 | 1 | |||
FBN3 | ENST00000601739.5 | c.8222T>C | p.Ile2741Thr | missense_variant | 64/64 | 1 | |||
FBN3 | ENST00000651877.1 | c.8348T>C | p.Ile2783Thr | missense_variant | 64/64 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461202Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726918
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 04, 2023 | The c.8222T>C (p.I2741T) alteration is located in exon 63 (coding exon 63) of the FBN3 gene. This alteration results from a T to C substitution at nucleotide position 8222, causing the isoleucine (I) at amino acid position 2741 to be replaced by a threonine (T). 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