rs371988433
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001458.5(FLNC):āc.4593C>Gā(p.Ile1531Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.4593C>G | p.Ile1531Met | missense_variant | 27/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.4593C>G | p.Ile1531Met | missense_variant | 27/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.4593C>G | p.Ile1531Met | missense_variant | 27/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.4593C>G | p.Ile1531Met | missense_variant | 27/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249302Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135300
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461642Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727148
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
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 | Mar 18, 2022 | This variant is present in population databases (rs371988433, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1531 of the FLNC protein (p.Ile1531Met). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 539443). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at