Variant 17-18245587-C-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_002018.4(FLII):c.3577G>A(p.Asp1193Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

FLII
NM_002018.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50

Variant links:

Genes affected

FLII (HGNC:3750): (FLII actin remodeling protein) This gene encodes a protein with a gelsolin-like actin binding domain and an N-terminal leucine-rich repeat-protein protein interaction domain. The protein is similar to a Drosophila protein involved in early embryogenesis and the structural organization of indirect flight muscle. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

FLII links:

FLII (HGNC:):

FLII 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
FLII	NM_002018.4 linkuse as main transcript	c.3577G>A	p.Asp1193Asn	missense_variant	28/30	ENST00000327031.9	NP_002009.1	Q13045-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLII	ENST00000327031.9 linkuse as main transcript	c.3577G>A	p.Asp1193Asn	missense_variant	28/30	1	NM_002018.4	ENSP00000324573.4		Q13045-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251362

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727172

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:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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 11, 2024

The c.3577G>A (p.D1193N) alteration is located in exon 28 (coding exon 28) of the FLII gene. This alteration results from a G to A substitution at nucleotide position 3577, causing the aspartic acid (D) at amino acid position 1193 to be replaced by an asparagine (N). 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

Benign

0.31

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.42

.;T;.;.;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.58

D;D;D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

.;M;.;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.2

.;D;.;.;.

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

.;D;.;.;.

Sift4G

Uncertain

0.0020

D;D;D;D;D

Polyphen

1.0

.;D;.;.;.

Vest4

0.64, 0.69, 0.68

MutPred

0.55

.;Gain of helix (P = 0.1736);.;.;.;

MVP

0.76

MPC

0.91

ClinPred

0.73

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.77

gMVP

0.62

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.

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