rs201810442
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate
The NM_001110556.2(FLNA):c.3602C>T(p.Ala1201Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,095,386 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: not found (cov: 25)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Consequence
FLNA
NM_001110556.2 missense
NM_001110556.2 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 1.24
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 Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), FLNA. . Gene score misZ 3.7802 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked Ehlers-Danlos syndrome, terminal osseous dysplasia-pigmentary defects syndrome, FG syndrome 2, frontometaphyseal dysplasia, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome, otopalatodigital syndrome type 2, periventricular nodular heterotopia, otopalatodigital syndrome type 1, intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked, familial thoracic aortic aneurysm and aortic dissection, congenital short bowel syndrome, frontometaphyseal dysplasia 1, cardiac valvular dysplasia, X-linked.
BP4
Computational evidence support a benign effect (MetaRNN=0.25945172).
BP6
Variant X-154360193-G-A is Benign according to our data. Variant chrX-154360193-G-A is described in ClinVar as [Benign]. Clinvar id is 583155.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.3602C>T | p.Ala1201Val | missense_variant | 22/48 | ENST00000369850.10 | NP_001104026.1 | |
FLNA | NM_001456.4 | c.3602C>T | p.Ala1201Val | missense_variant | 22/47 | NP_001447.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.3602C>T | p.Ala1201Val | missense_variant | 22/48 | 1 | NM_001110556.2 | ENSP00000358866.3 |
Frequencies
GnomAD3 genomes Cov.: 25
GnomAD3 genomes
Cov.:
25
GnomAD3 exomes AF: 0.00000557 AC: 1AN: 179568Hom.: 0 AF XY: 0.0000150 AC XY: 1AN XY: 66862
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GnomAD4 exome AF: 0.00000183 AC: 2AN: 1095386Hom.: 0 Cov.: 33 AF XY: 0.00000277 AC XY: 1AN XY: 361636
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GnomAD4 genome Cov.: 25
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jul 07, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.
FATHMM_MKL
Benign
N
LIST_S2
Pathogenic
D;D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;.
Sift4G
Uncertain
D;D;D;D;T
Polyphen
P;.;B;B;.
Vest4
MutPred
Loss of catalytic residue at A1201 (P = 0.1907);.;Loss of catalytic residue at A1201 (P = 0.1907);Loss of catalytic residue at A1201 (P = 0.1907);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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