rs782292045
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_001110556.2(FLNA):c.25G>T(p.Gly9Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,199,415 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001110556.2 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 |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.25G>T | p.Gly9Cys | missense_variant | 2/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.25G>T | p.Gly9Cys | missense_variant | 2/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.25G>T | p.Gly9Cys | missense_variant | 2/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000177 AC: 2AN: 113044Hom.: 0 Cov.: 25 AF XY: 0.0000284 AC XY: 1AN XY: 35192
GnomAD3 exomes AF: 0.000114 AC: 17AN: 149059Hom.: 0 AF XY: 0.000203 AC XY: 10AN XY: 49177
GnomAD4 exome AF: 0.0000534 AC: 58AN: 1086371Hom.: 0 Cov.: 32 AF XY: 0.0000927 AC XY: 33AN XY: 355901
GnomAD4 genome ? AF: 0.0000177 AC: 2AN: 113044Hom.: 0 Cov.: 25 AF XY: 0.0000284 AC XY: 1AN XY: 35192
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 22, 2015 | - - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 08, 2019 | The p.G9C variant (also known as c.25G>T), located in coding exon 1 of the FLNA gene, results from a G to T substitution at nucleotide position 25. The glycine at codon 9 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2022 | - - |
FLNA-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 07, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at