rs775206410
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP2BS2
The ENST00000316623.10(FBN1):āc.980G>Cā(p.Arg327Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/18 in silico tools predict 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. R327G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000316623.10 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FBN1 | NM_000138.5 | c.980G>C | p.Arg327Thr | missense_variant | 9/66 | ENST00000316623.10 | NP_000129.3 | |
FBN1 | NM_001406716.1 | c.980G>C | p.Arg327Thr | missense_variant | 8/65 | NP_001393645.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FBN1 | ENST00000316623.10 | c.980G>C | p.Arg327Thr | missense_variant | 9/66 | 1 | NM_000138.5 | ENSP00000325527 | P1 | |
FBN1 | ENST00000559133.6 | c.980G>C | p.Arg327Thr | missense_variant, NMD_transcript_variant | 9/67 | 1 | ENSP00000453958 | |||
FBN1 | ENST00000674301.2 | c.980G>C | p.Arg327Thr | missense_variant, NMD_transcript_variant | 9/68 | ENSP00000501333 | ||||
FBN1 | ENST00000537463.6 | c.636+11573G>C | intron_variant, NMD_transcript_variant | 5 | ENSP00000440294 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251400Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135864
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727216
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 25, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2024 | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12938084) - |
Marfan syndrome;C0265287:Acromicric dysplasia;C1858556:MASS syndrome;C1861456:Stiff skin syndrome;C1869115:Weill-Marchesani syndrome 2, dominant;C3280054:Geleophysic dysplasia 2;C3541518:Ectopia lentis 1, isolated, autosomal dominant;C4310796:Progeroid and marfanoid aspect-lipodystrophy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 01, 2021 | - - |
Marfan syndrome;C4707243:Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 06, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at