Variant 1-15777220-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017556.4(FBLIM1):c.941A>T(p.Asp314Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,940 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FBLIM1
NM_017556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

Variant links:

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]

FBLIM1 links:

Genome browser will be placed here

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

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBLIM1	NM_017556.4 link	c.941A>T	p.Asp314Val	missense_variant	8/9	ENST00000375766.8	NP_060026.2	Q8WUP2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBLIM1	ENST00000375766.8 link	c.941A>T	p.Asp314Val	missense_variant	8/9	2	NM_017556.4	ENSP00000364921.3		Q8WUP2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251244

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460940

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 03, 2024

The c.941A>T (p.D314V) alteration is located in exon 8 (coding exon 6) of the FBLIM1 gene. This alteration results from a A to T substitution at nucleotide position 941, causing the aspartic acid (D) at amino acid position 314 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

T;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.85

.;D;D

M_CAP

Benign

0.076

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.1

L;L;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.035

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.41

MutPred

0.59

Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);.;

MVP

0.86

ClinPred

0.82

GERP RS

4.9

Varity_R

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over