chr7-128846086-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_001458.5(FLNC):c.3887C>T(p.Ser1296Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,786 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1296W) has been classified as Uncertain significance.
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.3887C>T | p.Ser1296Leu | missense_variant | 22/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.3887C>T | p.Ser1296Leu | missense_variant | 22/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3887C>T | p.Ser1296Leu | missense_variant | 22/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.3887C>T | p.Ser1296Leu | missense_variant | 22/47 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000522 AC: 13AN: 249030Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135306
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461702Hom.: 0 Cov.: 34 AF XY: 0.0000234 AC XY: 17AN XY: 727166
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74302
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 | Aug 20, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 29, 2022 | 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 - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 2023 | The p.S1296L variant (also known as c.3887C>T), located in coding exon 22 of the FLNC gene, results from a C to T substitution at nucleotide position 3887. The serine at codon 1296 is replaced by leucine, an amino acid with dissimilar properties. 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at