chr1-15774709-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017556.4(FBLIM1):c.803C>A(p.Thr268Lys) variant causes a missense 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
FBLIM1
NM_017556.4 missense
NM_017556.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 2.02
Genes affected
FBLIM1 (HGNC:24686): (filamin binding LIM protein 1) This gene encodes a protein with an N-terminal filamin-binding domain, a central proline-rich domain, and, multiple C-terminal LIM domains. This protein localizes at cell junctions and may link cell adhesion structures to the actin cytoskeleton. This protein may be involved in the assembly and stabilization of actin-filaments and likely plays a role in modulating cell adhesion, cell morphology and cell motility. This protein also localizes to the nucleus and may affect cardiomyocyte differentiation after binding with the CSX/NKX2-5 transcription factor. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| FBLIM1 | ENST00000375766.8 | c.803C>A | p.Thr268Lys | missense_variant | 7/9 | 2 | NM_017556.4 | ENSP00000364921.3 | ||
| FBLIM1 | ENST00000441801.6 | c.803C>A | p.Thr268Lys | missense_variant | 6/6 | 1 | ENSP00000416387.2 | |||
| FBLIM1 | ENST00000375771.5 | c.803C>A | p.Thr268Lys | missense_variant | 8/10 | 1 | ENSP00000364926.1 | |||
| FBLIM1 | ENST00000332305.5 | c.512C>A | p.Thr171Lys | missense_variant | 3/5 | 2 | ENSP00000364920.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2024 | The c.803C>A (p.T268K) alteration is located in exon 6 (coding exon 5) of the FBLIM1 gene. This alteration results from a C to A substitution at nucleotide position 803, causing the threonine (T) at amino acid position 268 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;L;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;T;D
Sift4G
Benign
T;T;T;T
Polyphen
B;B;P;P
Vest4
MutPred
Gain of methylation at T268 (P = 0.0051);Gain of methylation at T268 (P = 0.0051);Gain of methylation at T268 (P = 0.0051);.;
MVP
MPC
0.30
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
Publications
No publications associated with this variant yet.