1-206868523-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_018724.4(IL20):c.490G>C(p.Glu164Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000281 in 1,603,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E164K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

IL20
NM_018724.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

IL20 (HGNC:6002): (interleukin 20) The protein encoded by this gene is a cytokine structurally related to interleukin 10 (IL10). This cytokine has been shown to transduce its signal through signal transducer and activator of transcription 3 (STAT3) in keratinocytes. A specific receptor for this cytokine is found to be expressed in skin and upregulated dramatically in psoriatic skin, suggesting a role for this protein in epidermal function and psoriasis. [provided by RefSeq, Jul 2008]

IL20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL20	NM_018724.4 linkuse as main transcript	c.490G>C	p.Glu164Gln	missense_variant	6/6	ENST00000367098.6
IL20	NM_001385166.1 linkuse as main transcript	c.490G>C	p.Glu164Gln	missense_variant	7/7
IL20	NM_001385167.1 linkuse as main transcript	c.490G>C	p.Glu164Gln	missense_variant	8/8
IL20	NM_001385165.1 linkuse as main transcript	c.415G>C	p.Glu139Gln	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL20	ENST00000367098.6 linkuse as main transcript	c.490G>C	p.Glu164Gln	missense_variant	6/6	1	NM_018724.4	P1	Q9NYY1-1
IL20	ENST00000367096.7 linkuse as main transcript	c.490G>C	p.Glu164Gln	missense_variant	5/5	1		P1	Q9NYY1-1
IL20	ENST00000391930.3 linkuse as main transcript	c.415G>C	p.Glu139Gln	missense_variant	4/4	1			Q9NYY1-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152106

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000495

AC:

AN:

242382

Hom.:

AF XY:

0.0000686

AC XY:

AN XY:

131164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000269

AC:

AN:

1451318

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

721774

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:

0.0000352

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000906

AC:

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 07, 2023

The c.490G>C (p.E164Q) alteration is located in exon 5 (coding exon 5) of the IL20 gene. This alteration results from a G to C substitution at nucleotide position 490, causing the glutamic acid (E) at amino acid position 164 to be replaced by a glutamine (Q). 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

0.69

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Uncertain

0.0

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;D;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.96

D;D;D

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.2

M;M;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.88

MutPred

0.90

Gain of catalytic residue at E164 (P = 0.0595);Gain of catalytic residue at E164 (P = 0.0595);.;

MVP

0.84

MPC

0.50

ClinPred

0.71

GERP RS

4.5

Varity_R

0.92

gMVP

0.65

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