NM_018724.4:c.476T>C

Variant names:

• chr1-206868509-T-C
• rs1175170031
• NM_018724.4:c.476T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018724.4(IL20):​c.476T>C​(p.Val159Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL20 NM_018724.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3667137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018724.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL20	NM_018724.4	MANE Select	c.476T>C	p.Val159Ala	missense	Exon 6 of 6	NP_061194.2
	IL20	NM_001385166.1		c.476T>C	p.Val159Ala	missense	Exon 7 of 7	NP_001372095.1	Q9NYY1-1
	IL20	NM_001385167.1		c.476T>C	p.Val159Ala	missense	Exon 8 of 8	NP_001372096.1	Q9NYY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL20	ENST00000367098.6	TSL:1 MANE Select	c.476T>C	p.Val159Ala	missense	Exon 6 of 6	ENSP00000356065.1	Q9NYY1-1
	IL20	ENST00000367096.7	TSL:1	c.476T>C	p.Val159Ala	missense	Exon 5 of 5	ENSP00000356063.3	Q9NYY1-1
	IL20	ENST00000391930.3	TSL:1	c.401T>C	p.Val134Ala	missense	Exon 4 of 4	ENSP00000375796.2	Q9NYY1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.90	P
Vest4		0.30
MutPred		0.62		Loss of methylation at K160 (P = 0.0425)
MVP		0.90
MPC		0.47
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.40
gMVP		0.19
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs1175170031; hg19: chr1-207041854;