rs782359458
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP2PP3_Strong
The NM_001110556.2(FLNA):c.5786C>T(p.Pro1929Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,210,271 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a pathogenic 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. P1929S) 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.5786C>T | p.Pro1929Leu | missense_variant | 36/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.5762C>T | p.Pro1921Leu | missense_variant | 35/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.5786C>T | p.Pro1929Leu | missense_variant | 36/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000885 AC: 1AN: 113029Hom.: 0 Cov.: 25 AF XY: 0.0000284 AC XY: 1AN XY: 35157
GnomAD3 exomes AF: 0.0000165 AC: 3AN: 181605Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67203
GnomAD4 exome AF: 0.0000182 AC: 20AN: 1097242Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 6AN XY: 362824
GnomAD4 genome ? AF: 0.00000885 AC: 1AN: 113029Hom.: 0 Cov.: 25 AF XY: 0.0000284 AC XY: 1AN XY: 35157
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 09, 2021 | The c.5762C>T (p.P1921L) alteration is located in exon 35 (coding exon 34) of the FLNA gene. This alteration results from a C to T substitution at nucleotide position 5762, causing the proline (P) at amino acid position 1921 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 570943; Landrum et al., 2016) - |
FLNA-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 23, 2023 | The FLNA c.5786C>T variant is predicted to result in the amino acid substitution p.Pro1929Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0073% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-153581996-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at