rs1555398992
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3_Moderate
The NM_000138.5(FBN1):c.2752C>T(p.Pro918Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,282 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P918R) 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.2752C>T | p.Pro918Ser | missense_variant | 24/66 | ENST00000316623.10 | |
FBN1 | NM_001406716.1 | c.2752C>T | p.Pro918Ser | missense_variant | 23/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.2752C>T | p.Pro918Ser | missense_variant | 24/66 | 1 | NM_000138.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455282Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 724330
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 07, 2023 | - - |
Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 527166). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 918 of the FBN1 protein (p.Pro918Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at