rs371398126
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_001458.5(FLNC):c.2404G>A(p.Gly802Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G802R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.2404G>A | p.Gly802Ser | missense_variant | 16/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.2404G>A | p.Gly802Ser | missense_variant | 16/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.2404G>A | p.Gly802Ser | missense_variant | 16/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.2404G>A | p.Gly802Ser | missense_variant | 16/47 | 1 | A1 | ||
FLNC | ENST00000388853.3 | n.520G>A | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248672Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135172
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461392Hom.: 0 Cov.: 37 AF XY: 0.0000165 AC XY: 12AN XY: 727022
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74360
ClinVar
Submissions by phenotype
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 24, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 13, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 16, 2021 | The p.G802S variant (also known as c.2404G>A), located in coding exon 16 of the FLNC gene, results from a G to A substitution at nucleotide position 2404. The glycine at codon 802 is replaced by serine, an amino acid with similar 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 802 of the FLNC protein (p.Gly802Ser). This variant is present in population databases (rs371398126, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 472011). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at