rs113604459
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP2PP3_ModeratePP5
The NM_000138.5(FBN1):c.202T>C(p.Cys68Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 10/17 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C68Y) 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 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.202T>C | p.Cys68Arg | missense_variant | 3/66 | ENST00000316623.10 | |
FBN1 | NM_001406716.1 | c.202T>C | p.Cys68Arg | missense_variant | 2/65 | ||
FBN1 | NM_001406717.1 | c.202T>C | p.Cys68Arg | missense_variant | 3/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.202T>C | p.Cys68Arg | missense_variant | 3/66 | 1 | NM_000138.5 | P1 | |
FBN1 | ENST00000559133.6 | c.202T>C | p.Cys68Arg | missense_variant, NMD_transcript_variant | 3/67 | 1 | |||
FBN1 | ENST00000674301.2 | c.202T>C | p.Cys68Arg | missense_variant, NMD_transcript_variant | 3/68 | ||||
FBN1 | ENST00000537463.6 | c.202T>C | p.Cys68Arg | missense_variant, NMD_transcript_variant | 3/31 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Marfan syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Sangiuolo Lab - Medical Genetics Laboratory, Tor Vergata University | Jun 06, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at