rs373908435
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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.3036G>A(p.Ser1012=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,209,166 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 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 0.000036 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.00014 ( 0 hom. 41 hem. )
Consequence
FLNA
NM_001110556.2 synonymous
NM_001110556.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.46
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=-0.84).
BP6
?
Variant X-154361479-C-T is Benign according to our data. Variant chrX-154361479-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-5.46 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 41 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.3036G>A | p.Ser1012= | synonymous_variant | 21/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.3036G>A | p.Ser1012= | synonymous_variant | 21/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.3036G>A | p.Ser1012= | synonymous_variant | 21/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000359 AC: 4AN: 111539Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33707
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GnomAD3 exomes AF: 0.0000496 AC: 9AN: 181435Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67457
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GnomAD4 exome AF: 0.000141 AC: 155AN: 1097627Hom.: 0 Cov.: 33 AF XY: 0.000113 AC XY: 41AN XY: 363177
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GnomAD4 genome ? AF: 0.0000359 AC: 4AN: 111539Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33707
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 27, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 03, 2022 | 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 04, 2022 | - - |
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