rs753591663
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The ENST00000325888.13(FLNC):āc.3871C>Gā(p.Arg1291Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,954 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. R1291H) has been classified as Likely benign.
Frequency
Consequence
ENST00000325888.13 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.3871C>G | p.Arg1291Gly | missense_variant | 22/48 | ENST00000325888.13 | NP_001449.3 | |
FLNC | NM_001127487.2 | c.3871C>G | p.Arg1291Gly | missense_variant | 22/47 | NP_001120959.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3871C>G | p.Arg1291Gly | missense_variant | 22/48 | 1 | NM_001458.5 | ENSP00000327145 | P3 | |
FLNC | ENST00000346177.6 | c.3871C>G | p.Arg1291Gly | missense_variant | 22/47 | 1 | ENSP00000344002 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248848Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135262
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461690Hom.: 0 Cov.: 34 AF XY: 0.0000193 AC XY: 14AN XY: 727160
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74440
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 12, 2023 | The p.R1291G variant (also known as c.3871C>G), located in coding exon 22 of the FLNC gene, results from a C to G substitution at nucleotide position 3871. The arginine at codon 1291 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at