1-206866559-C-A

Variant names:

• chr1-206866559-C-A
• NM_018724.4:c.301C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018724.4(IL20):​c.301C>A​(p.Pro101Thr) 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. 15/21 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: -1.05

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06084448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20	NM_018724.4	c.301C>A	p.Pro101Thr	missense_variant	Exon 4 of 6	ENST00000367098.6	NP_061194.2
IL20	NM_001385166.1	c.301C>A	p.Pro101Thr	missense_variant	Exon 5 of 7		NP_001372095.1
IL20	NM_001385167.1	c.301C>A	p.Pro101Thr	missense_variant	Exon 6 of 8		NP_001372096.1
IL20	NM_001385165.1	c.301C>A	p.Pro101Thr	missense_variant	Exon 4 of 5		NP_001372094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL20	ENST00000367098.6	c.301C>A	p.Pro101Thr	missense_variant	Exon 4 of 6	1	NM_018724.4	ENSP00000356065.1
IL20	ENST00000367096.7	c.301C>A	p.Pro101Thr	missense_variant	Exon 3 of 5	1		ENSP00000356063.3
IL20	ENST00000391930.3	c.301C>A	p.Pro101Thr	missense_variant	Exon 3 of 4	1		ENSP00000375796.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.301C>A (p.P101T) alteration is located in exon 3 (coding exon 3) of the IL20 gene. This alteration results from a C to A substitution at nucleotide position 301, causing the proline (P) at amino acid position 101 to be replaced by a threonine (T). 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	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.96
DANN	Benign	0.32
DEOGEN2	Benign	0.090	T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.61	.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.0090
Sift	Benign	0.63	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.10	B;B;.
Vest4		0.19
MutPred		0.43		Gain of catalytic residue at P101 (P = 0.0307);Gain of catalytic residue at P101 (P = 0.0307);Gain of catalytic residue at P101 (P = 0.0307);
MVP		0.31
MPC		0.12
ClinPred		0.038	T
GERP RS		-3.4
Varity_R		0.18
gMVP		0.17

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.

Other links and lift over

hg19: chr1-207039904;