7-128854580-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001458.5(FLNC):c.6895G>C(p.Gly2299Arg) 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. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.6895G>C | p.Gly2299Arg | missense_variant | Exon 41 of 48 | ENST00000325888.13 | NP_001449.3 | |
FLNC | NM_001127487.2 | c.6796G>C | p.Gly2266Arg | missense_variant | Exon 40 of 47 | NP_001120959.1 | ||
FLNC-AS1 | NR_149055.1 | n.103-1183C>G | intron_variant | Intron 1 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.6895G>C | p.Gly2299Arg | missense_variant | Exon 41 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.6796G>C | p.Gly2266Arg | missense_variant | Exon 40 of 47 | 1 | ENSP00000344002.6 | |||
FLNC-AS1 | ENST00000469965.1 | n.103-1183C>G | intron_variant | Intron 1 of 3 | 4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000421 AC: 1AN: 237432Hom.: 0 AF XY: 0.00000772 AC XY: 1AN XY: 129578
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
The G2299R variant in the FLNC gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G2299R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G2299R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G2299R as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at