rs200928780
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001458.5(FLNC):c.3853G>A(p.Gly1285Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3853G>A | p.Gly1285Ser | missense_variant | Exon 22 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.3853G>A | p.Gly1285Ser | missense_variant | Exon 22 of 47 | 1 | ENSP00000344002.6 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248868Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135252
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461738Hom.: 0 Cov.: 34 AF XY: 0.0000248 AC XY: 18AN XY: 727182
GnomAD4 genome AF: 0.000112 AC: 17AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74472
ClinVar
Submissions by phenotype
not provided Uncertain:3
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function -
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BS2 -
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26 Uncertain:1
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Cardiovascular phenotype Uncertain:1
The p.G1285S variant (also known as c.3853G>A), located in coding exon 22 of the FLNC gene, results from a G to A substitution at nucleotide position 3853. The glycine at codon 1285 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available 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. -
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at