rs140857707
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001458.5(FLNC):c.5468C>T(p.Thr1823Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,613,326 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).
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.5468C>T | p.Thr1823Met | missense_variant | Exon 33 of 48 | ENST00000325888.13 | NP_001449.3 | |
FLNC | NM_001127487.2 | c.5369C>T | p.Thr1790Met | missense_variant | Exon 32 of 47 | NP_001120959.1 | ||
FLNC-AS1 | NR_149055.1 | n.316-467G>A | intron_variant | Intron 3 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.5468C>T | p.Thr1823Met | missense_variant | Exon 33 of 48 | 1 | NM_001458.5 | ENSP00000327145.8 | ||
FLNC | ENST00000346177.6 | c.5369C>T | p.Thr1790Met | missense_variant | Exon 32 of 47 | 1 | ENSP00000344002.6 | |||
FLNC-AS1 | ENST00000469965.1 | n.316-467G>A | intron_variant | Intron 3 of 3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000858 AC: 13AN: 151574Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249524Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135382
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461634Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 15AN XY: 727136
GnomAD4 genome AF: 0.0000857 AC: 13AN: 151692Hom.: 0 Cov.: 32 AF XY: 0.0000945 AC XY: 7AN XY: 74082
ClinVar
Submissions by phenotype
not provided Uncertain:4
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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.T1823M variant (also known as c.5468C>T), located in coding exon 33 of the FLNC gene, results from a C to T substitution at nucleotide position 5468. The threonine at codon 1823 is replaced by methionine, an amino acid with similar properties. This alteration has been reported in a myofibrillar myopathy cohort in an individual with a normal cardiac evaluation (Luo YB et al. Front Neurol, 2020 Sep;11:1014). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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