rs727505110
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_000138.5(FBN1):āc.2942G>Cā(p.Cys981Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 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 Likely pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C981Y) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000138.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.2942G>C | p.Cys981Ser | missense_variant | 25/66 | ENST00000316623.10 | |
FBN1 | NM_001406716.1 | c.2942G>C | p.Cys981Ser | missense_variant | 24/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.2942G>C | p.Cys981Ser | missense_variant | 25/66 | 1 | NM_000138.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Marfan syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 09, 2014 | The Cys981Ser variant in FBN1 has been reported in two individuals with clinical features of Marfan syndrome, 1 in which occured de novo (Sakai 2006; LMM unpubl ished data). It was absent from large population studies. Computational predicti on tools and conservation analysis suggest that this variant may impact the prot ein, though this information is not predictive enough to determine pathogenicity . In summary, although additional studies are required to fully establish its cl inical significance, the Cys981Ser variant is likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at