rs363803
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3_Moderate
The NM_000138.5(FBN1):āc.6068T>Cā(p.Ile2023Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. I2023I) has been classified as Likely benign.
Frequency
Consequence
NM_000138.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.6068T>C | p.Ile2023Thr | missense_variant | 50/66 | ENST00000316623.10 | |
FBN1 | NM_001406716.1 | c.6068T>C | p.Ile2023Thr | missense_variant | 49/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.6068T>C | p.Ile2023Thr | missense_variant | 50/66 | 1 | NM_000138.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461314Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726974
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 05, 2014 | The p.I2023T variant (also known as c.6068T>C), located in coding exon 49 of the FBN1 gene in the cb EGF-like #31 domain, results from a T to C substitution at nucleotide position 6068. The isoleucine at codon 2023 is replaced by threonine, an amino acid with some similar properties. This alteration was reported in a study of patients screened for FBN1 mutations with either definitive Marfan syndrome or related phenotypes (Liu WO et al. Genet Test. 1997-1998;1(4):237-242), however a detailed phenotype of the patient identified with this alteration was not reported. This variant was also previously reported in the SNPDatabase as rs363803. This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. Based on protein sequence alignment, this amino acid position is conserved in available vertebrate species except for tenrec and lamprey. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at