rs778781499
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001458.5(FLNC):c.2130C>A(p.Asp710Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. D710N) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.2130C>A | p.Asp710Glu | missense_variant | 14/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.2130C>A | p.Asp710Glu | missense_variant | 14/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.2130C>A | p.Asp710Glu | missense_variant | 14/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.2130C>A | p.Asp710Glu | missense_variant | 14/47 | 1 | A1 | ||
FLNC | ENST00000388853.3 | n.246C>A | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 33
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 | Apr 11, 2018 | Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with FLNC-related disease. This sequence change replaces aspartic acid with glutamic acid at codon 710 of the FLNC protein (p.Asp710Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at