rs1557180226
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000369856.8(FLNA):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 25)
Consequence
FLNA
ENST00000369856.8 start_lost
ENST00000369856.8 start_lost
Scores
5
8
4
Clinical Significance
Conservation
PhyloP100: 2.22
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 Pathogenic. Variant got 11 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 17 pathogenic variants. Next in-frame start position is after 62 codons. Genomic position: 154370981. Lost 0.023 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-154371164-T-C is Pathogenic according to our data. Variant chrX-154371164-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 488068.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 25
GnomAD3 genomes
Cov.:
25
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 25
GnomAD4 genome
Cov.:
25
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Heterotopia, periventricular, X-linked dominant Pathogenic:1
-
Clinical Genetics Group, University of Otago
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
D;.;.;.;.
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;D;T;T;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;L;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.
Sift4G
Benign
T;D;T;T;D
Polyphen
B;.;P;P;.
Vest4
MutPred
Loss of loop (P = 0.0804);.;Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at