rs371591881
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4BP6_Very_StrongBS2
The NM_001458.5(FLNC):āc.4334A>Gā(p.Lys1445Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,614,130 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 Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. K1445K) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.4334A>G | p.Lys1445Arg | missense_variant | 25/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.4334A>G | p.Lys1445Arg | missense_variant | 25/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.4334A>G | p.Lys1445Arg | missense_variant | 25/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.4334A>G | p.Lys1445Arg | missense_variant | 25/47 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 249324Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135316
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461818Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727210
GnomAD4 genome AF: 0.000125 AC: 19AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74468
ClinVar
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2020 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at