rs1208353421
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001110556.2(FLNA):c.2571G>A(p.Thr857Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,208,881 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.000024 ( 0 hom. 8 hem. )
Consequence
FLNA
NM_001110556.2 synonymous
NM_001110556.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.74
Genes affected
FLNA (HGNC:3754): (filamin A) The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant X-154362327-C-T is Benign according to our data. Variant chrX-154362327-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-154362327-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.74 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.2571G>A | p.Thr857Thr | synonymous_variant | 18/48 | ENST00000369850.10 | NP_001104026.1 | |
FLNA | NM_001456.4 | c.2571G>A | p.Thr857Thr | synonymous_variant | 18/47 | NP_001447.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.2571G>A | p.Thr857Thr | synonymous_variant | 18/48 | 1 | NM_001110556.2 | ENSP00000358866.3 |
Frequencies
GnomAD3 genomes AF: 0.0000625 AC: 7AN: 111911Hom.: 0 Cov.: 24 AF XY: 0.0000587 AC XY: 2AN XY: 34083
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GnomAD3 exomes AF: 0.0000277 AC: 5AN: 180739Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67189
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GnomAD4 exome AF: 0.0000237 AC: 26AN: 1096970Hom.: 0 Cov.: 32 AF XY: 0.0000221 AC XY: 8AN XY: 362676
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GnomAD4 genome AF: 0.0000625 AC: 7AN: 111911Hom.: 0 Cov.: 24 AF XY: 0.0000587 AC XY: 2AN XY: 34083
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ClinVar
Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 13, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 24, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | FLNA: BP4, BP7, BS2 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 17, 2017 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 19, 2020 | 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. - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Dec 19, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at