Variant 1-206866545-A-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_018724.4(IL20):c.287A>T(p.Lys96Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,840 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: 0.0000068 ( 0 hom. )

Consequence

IL20
NM_018724.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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:

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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
IL20	NM_018724.4 linkuse as main transcript	c.287A>T	p.Lys96Ile	missense_variant	4/6	ENST00000367098.6
IL20	NM_001385166.1 linkuse as main transcript	c.287A>T	p.Lys96Ile	missense_variant	5/7
IL20	NM_001385167.1 linkuse as main transcript	c.287A>T	p.Lys96Ile	missense_variant	6/8
IL20	NM_001385165.1 linkuse as main transcript	c.287A>T	p.Lys96Ile	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL20	ENST00000367098.6 linkuse as main transcript	c.287A>T	p.Lys96Ile	missense_variant	4/6	1	NM_018724.4	P1	Q9NYY1-1
IL20	ENST00000367096.7 linkuse as main transcript	c.287A>T	p.Lys96Ile	missense_variant	3/5	1		P1	Q9NYY1-1
IL20	ENST00000391930.3 linkuse as main transcript	c.287A>T	p.Lys96Ile	missense_variant	3/4	1			Q9NYY1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727230

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

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

May 24, 2023

The c.287A>T (p.K96I) alteration is located in exon 3 (coding exon 3) of the IL20 gene. This alteration results from a A to T substitution at nucleotide position 287, causing the lysine (K) at amino acid position 96 to be replaced by an isoleucine (I). 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

Uncertain

0.46

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.82

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.1

M;M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.52

MVP

0.83

MPC

0.65

ClinPred

1.0

GERP RS

5.1

Varity_R

0.78

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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