chrX-154348865-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001110556.2(FLNA):c.7928G>C(p.Arg2643Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R2643C) has been classified as Likely benign.
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.7928G>C | p.Arg2643Pro | missense_variant | 48/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.7904G>C | p.Arg2635Pro | missense_variant | 47/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.7928G>C | p.Arg2643Pro | missense_variant | 48/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes Cov.: 25
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 25
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 | Labcorp Genetics (formerly Invitae), Labcorp | Oct 08, 2021 | 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. This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 2635 of the FLNA protein (p.Arg2635Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.