rs137854472
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM1PP2BP4BP6
The NM_000138.5(FBN1):c.3128A>G(p.Lys1043Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K1043N) has been classified as Uncertain significance.
Frequency
Consequence
NM_000138.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.3128A>G | p.Lys1043Arg | missense_variant | 26/66 | ENST00000316623.10 | |
FBN1 | NM_001406716.1 | c.3128A>G | p.Lys1043Arg | missense_variant | 25/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.3128A>G | p.Lys1043Arg | missense_variant | 26/66 | 1 | NM_000138.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251474Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461850Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727228
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neonatal Marfan syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1997 | - - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 2018 | The p.K1043R variant (also known as c.3128A>G), located in coding exon 25 of the FBN1 gene, results from an A to G substitution at nucleotide position 3128. The lysine at codon 1043 is replaced by arginine, an amino acid with highly similar properties. This alteration has been reported in a neonatal Marfan syndrome case; however, it has also been detected in a mitochondrial cytopathy individual and her healthy mother (Wang M et al. Hum. Mutat. 1997;9:359-62; Kohda M et al. PLoS Genet. 2016;12:e1005679). This amino acid position is not well conserved in available vertebrate species, and arginine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at