rs267606798
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Very_Strong
The NM_000138.5(FBN1):c.4781G>A(p.Gly1594Asp) 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. 11/18 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1594C) 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 17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.4781G>A | p.Gly1594Asp | missense_variant | 39/66 | ENST00000316623.10 | |
FBN1 | NM_001406716.1 | c.4781G>A | p.Gly1594Asp | missense_variant | 38/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.4781G>A | p.Gly1594Asp | missense_variant | 39/66 | 1 | NM_000138.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
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 | Jun 01, 2009 | - - |
Weill-Marchesani syndrome 2, dominant Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular and Physiopathological Bases of Osteochondrodysplasia, Imagine Institute | Jun 29, 2023 | - - |
Stiff skin syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 12, 2001 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at