chr7-128840604-G-A
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001458.5(FLNC):c.1606G>A(p.Glu536Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000113 in 1,614,240 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign 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. E536G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.1606G>A | p.Glu536Lys | missense_variant | 10/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.1606G>A | p.Glu536Lys | missense_variant | 10/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.1606G>A | p.Glu536Lys | missense_variant | 10/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.1606G>A | p.Glu536Lys | missense_variant | 10/47 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000721 AC: 18AN: 249572Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135406
GnomAD4 exome AF: 0.000113 AC: 165AN: 1461876Hom.: 2 Cov.: 33 AF XY: 0.000102 AC XY: 74AN XY: 727238
GnomAD4 genome AF: 0.000118 AC: 18AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74514
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 28, 2021 | - - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 25, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 04, 2022 | 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 | Jan 03, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at