Genetic Variant NM_017620.3:c.2539G>A (chr19-10688654-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017620.3(ILF3):c.2539G>A(p.Gly847Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000738 in 1,219,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000074 ( 0 hom. )

Consequence

ILF3
NM_017620.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

Publications

0 publications found

Variant links:

Genes affected

ILF3 (HGNC:6038): (interleukin enhancer binding factor 3) This gene encodes a double-stranded RNA (dsRNA) binding protein that complexes with other proteins, dsRNAs, small noncoding RNAs, and mRNAs to regulate gene expression and stabilize mRNAs. This protein (NF90, ILF3) forms a heterodimer with a 45 kDa transcription factor (NF45, ILF2) required for T-cell expression of interleukin 2. This complex has been shown to affect the redistribution of nuclear mRNA to the cytoplasm. Knockdown of NF45 or NF90 protein retards cell growth, possibly by inhibition of mRNA stabilization. In contrast, an isoform (NF110) of this gene that is predominantly restricted to the nucleus has only minor effects on cell growth when its levels are reduced. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Dec 2014]

ILF3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04097268).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILF3	NM_017620.3 link	c.2539G>A	p.Gly847Ser	missense_variant	Exon 19 of 20	ENST00000588657.6	NP_060090.2	Q12906-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILF3	ENST00000588657.6 link	c.2539G>A	p.Gly847Ser	missense_variant	Exon 19 of 20	5	NM_017620.3	ENSP00000468181.1		Q12906-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000738

AC:

AN:

1219472

Hom.:

Cov.:

AF XY:

0.00000508

AC XY:

AN XY:

590494

show subpopulations

African (AFR)

AF:

0.0000396

AC:

AN:

25278

American (AMR)

AF:

0.0000537

AC:

AN:

18622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16514

East Asian (EAS)

AF:

0.00

AC:

AN:

30824

South Asian (SAS)

AF:

0.0000231

AC:

AN:

43348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44438

Middle Eastern (MID)

AF:

0.000209

AC:

AN:

4776

European-Non Finnish (NFE)

AF:

0.00000507

AC:

AN:

986702

Other (OTH)

AF:

0.00

AC:

AN:

48970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2539G>A (p.G847S) alteration is located in exon 19 (coding exon 18) of the ILF3 gene. This alteration results from a G to A substitution at nucleotide position 2539, causing the glycine (G) at amino acid position 847 to be replaced by a serine (S). 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

0.058

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.14

.;.;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.63

T;.;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.041

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.60

.;.;N;.

PhyloP100

1.2

PrimateAI

Benign

0.37

PROVEAN

Benign

0.14

N;.;.;.

REVEL

Benign

0.028

Sift

Benign

0.59

T;.;.;.

Sift4G

Benign

0.065

T;T;D;T

Polyphen

0.0040

.;.;B;.

Vest4

0.31

MutPred

0.23

.;.;Gain of phosphorylation at G843 (P = 0.0079);.;

MVP

0.26

MPC

0.31

ClinPred

0.10

GERP RS

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.63

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over