chrX-154362500-C-G
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP6_Moderate
The NM_001110556.2(FLNA):āc.2483G>Cā(p.Arg828Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,197 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: not found (cov: 24)
Exomes š: 0.0000064 ( 0 hom. 1 hem. )
Consequence
FLNA
NM_001110556.2 missense
NM_001110556.2 missense
Scores
10
7
Clinical Significance
Conservation
PhyloP100: 1.71
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.
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.
BP6
Variant X-154362500-C-G is Benign according to our data. Variant chrX-154362500-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 533586.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.2483G>C | p.Arg828Pro | missense_variant | 17/48 | ENST00000369850.10 | NP_001104026.1 | |
FLNA | NM_001456.4 | c.2483G>C | p.Arg828Pro | missense_variant | 17/47 | NP_001447.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.2483G>C | p.Arg828Pro | missense_variant | 17/48 | 1 | NM_001110556.2 | ENSP00000358866 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
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24
GnomAD3 exomes AF: 0.00000552 AC: 1AN: 181129Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67429
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GnomAD4 exome AF: 0.00000638 AC: 7AN: 1097197Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1AN XY: 362905
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GnomAD4 genome Cov.: 24
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ClinVar
Significance: Likely 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
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 15, 2023 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;.;N;N;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;.
REVEL
Uncertain
Sift
Benign
T;.;T;T;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;B;B;.
Vest4
MutPred
Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP
MPC
ClinPred
T
GERP RS
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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