Variant chr19-10678633-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_017620.3(ILF3):c.580C>T(p.Pro194Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ILF3
NM_017620.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12

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 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
ILF3	NM_017620.3 linkuse as main transcript	c.580C>T	p.Pro194Ser	missense_variant	6/20	ENST00000588657.6	NP_060090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILF3	ENST00000588657.6 linkuse as main transcript	c.580C>T	p.Pro194Ser	missense_variant	6/20	5	NM_017620.3	ENSP00000468181	P3	Q12906-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460160

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726452

show subpopulations

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:

9.00e-7

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

Mar 30, 2024

The c.580C>T (p.P194S) alteration is located in exon 6 (coding exon 5) of the ILF3 gene. This alteration results from a C to T substitution at nucleotide position 580, causing the proline (P) at amino acid position 194 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

0.21

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

.;.;.;T;.;.;.;D

Eigen

Benign

-0.064

Eigen_PC

Benign

0.052

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;.;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.51

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.6

M;M;M;.;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.7

D;D;.;.;D;.;.;.

REVEL

Benign

0.22

Sift

Benign

0.056

T;D;.;.;D;.;.;.

Sift4G

Uncertain

0.059

T;T;T;T;T;T;T;T

Polyphen

0.44, 0.14, 0.081, 0.019, 0.37

.;B;B;.;B;B;.;B

Vest4

0.16

MutPred

0.68

Loss of catalytic residue at P194 (P = 0.0245);Loss of catalytic residue at P194 (P = 0.0245);Loss of catalytic residue at P194 (P = 0.0245);Loss of catalytic residue at P194 (P = 0.0245);Loss of catalytic residue at P194 (P = 0.0245);Loss of catalytic residue at P194 (P = 0.0245);Loss of catalytic residue at P194 (P = 0.0245);Loss of catalytic residue at P194 (P = 0.0245);

MVP

0.66

MPC

1.3

ClinPred

0.93

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.64

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