chr19-8066127-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032447.5(FBN3):āc.8222T>Cā(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 (ā ). 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