Variant 11-128694265-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002017.5(FLI1):c.7G>A(p.Gly3Arg) variant causes a missense change involving the alteration of a 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FLI1
NM_002017.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.42

Variant links:

Genes affected

FLI1 (HGNC:3749): (Fli-1 proto-oncogene, ETS transcription factor) This gene encodes a transcription factor containing an ETS DNA-binding domain. The gene can undergo a t(11;22)(q24;q12) translocation with the Ewing sarcoma gene on chromosome 22, which results in a fusion gene that is present in the majority of Ewing sarcoma cases. An acute lymphoblastic leukemia-associated t(4;11)(q21;q23) translocation involving this gene has also been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

FLI1 links:

SENCR (HGNC:44177): (smooth muscle and endothelial cell enriched migration/differentiation-associated lncRNA)

SENCR links:

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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

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLI1	NM_002017.5 link	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 9	ENST00000527786.7	NP_002008.2	Q01543-1A0A024R3M5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLI1	ENST00000527786.7 link	c.7G>A	p.Gly3Arg	missense_variant	Exon 1 of 9	1	NM_002017.5	ENSP00000433488.2		Q01543-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1285506

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

631252

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:

0.00

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 provided

Uncertain:1

Apr 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 3 of the FLI1 protein (p.Gly3Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FLI1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.1

Sift

Benign

0.064

Sift4G

Uncertain

0.034

Polyphen

0.38

Vest4

0.66

MutPred

0.22

Gain of solvent accessibility (P = 0.019);

MVP

0.69

MPC

0.52

ClinPred

0.87

GERP RS

4.4

Varity_R

0.12

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over