rs1557179001
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001110556.2(FLNA):c.1479G>C(p.Lys493Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K493R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.1479G>C | p.Lys493Asn | missense_variant | 10/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.1479G>C | p.Lys493Asn | missense_variant | 10/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.1479G>C | p.Lys493Asn | missense_variant | 10/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLNA protein function. ClinVar contains an entry for this variant (Variation ID: 464974). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 493 of the FLNA protein (p.Lys493Asn). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2021 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
FG syndrome 2 Benign:1
Likely benign, no assertion criteria provided | clinical testing | Service de Génétique Moléculaire, Hôpital Robert Debré | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at