rs200169573
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The NM_001458.5(FLNC):c.3242C>T(p.Ala1081Val) variant causes a missense change. The variant allele was found at a frequency of 0.000117 in 1,613,704 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. A1081T) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.3242C>T | p.Ala1081Val | missense_variant | 21/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.3242C>T | p.Ala1081Val | missense_variant | 21/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.3242C>T | p.Ala1081Val | missense_variant | 21/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.3242C>T | p.Ala1081Val | missense_variant | 21/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000137 AC: 34AN: 249024Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135218
GnomAD4 exome AF: 0.000113 AC: 165AN: 1461380Hom.: 0 Cov.: 32 AF XY: 0.0000990 AC XY: 72AN XY: 727044
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2021 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar by another clinical laboratory as a variant of uncertain significance (ClinVar Variant ID 539449; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 12, 2019 | - - |
Hypertrophic cardiomyopathy 26 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 24, 2019 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3,BS1. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 15, 2022 | The p.A1081V variant (also known as c.3242C>T), located in coding exon 21 of the FLNC gene, results from a C to T substitution at nucleotide position 3242. The alanine at codon 1081 is replaced by valine, 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at