chrX-154362500-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP6_Moderate

The NM_001110556.2(FLNA):ā€‹c.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

Scores

10
7

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.71
Variant links:
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]

Genome browser will be placed here

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
FLNANM_001110556.2 linkuse as main transcriptc.2483G>C p.Arg828Pro missense_variant 17/48 ENST00000369850.10 NP_001104026.1
FLNANM_001456.4 linkuse as main transcriptc.2483G>C p.Arg828Pro missense_variant 17/47 NP_001447.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FLNAENST00000369850.10 linkuse as main transcriptc.2483G>C p.Arg828Pro missense_variant 17/481 NM_001110556.2 ENSP00000358866 P21333-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD3 exomes
AF:
0.00000552
AC:
1
AN:
181129
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67429
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000638
AC:
7
AN:
1097197
Hom.:
0
Cov.:
33
AF XY:
0.00000276
AC XY:
1
AN XY:
362905
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000832
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 15, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.58
D;.;.;.;.
FATHMM_MKL
Benign
0.52
D
LIST_S2
Uncertain
0.88
D;D;.;D;D
M_CAP
Benign
0.063
D
MetaRNN
Uncertain
0.53
D;D;D;D;D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
-0.73
N;.;N;N;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.9
N;.;N;N;.
REVEL
Uncertain
0.56
Sift
Benign
0.20
T;.;T;T;.
Sift4G
Benign
0.31
T;T;T;T;T
Polyphen
0.88
P;.;B;B;.
Vest4
0.67
MutPred
0.54
Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP
0.93
MPC
0.76
ClinPred
0.24
T
GERP RS
4.9
Varity_R
0.78
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1347740802; hg19: chrX-153590868; API