rs573899913
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_001458.5(FLNC):āc.5363T>Gā(p.Val1788Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,792 control chromosomes in the GnomAD database, including 1 homozygotes. 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. V1788F) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.5363T>G | p.Val1788Gly | missense_variant | 32/48 | ENST00000325888.13 | |
FLNC-AS1 | NR_149055.1 | n.316-43A>C | intron_variant, non_coding_transcript_variant | ||||
FLNC | NM_001127487.2 | c.5264T>G | p.Val1755Gly | missense_variant | 31/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.5363T>G | p.Val1788Gly | missense_variant | 32/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.5264T>G | p.Val1755Gly | missense_variant | 31/47 | 1 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.316-43A>C | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000922 AC: 23AN: 249350Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135274
GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461620Hom.: 1 Cov.: 33 AF XY: 0.0000729 AC XY: 53AN XY: 727128
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 28, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2020 | 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 - |
Uncertain significance, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2022 | The p.V1788G variant (also known as c.5363T>G), located in coding exon 32 of the FLNC gene, results from a T to G substitution at nucleotide position 5363. The valine at codon 1788 is replaced by glycine, 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 | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at