1-206866546-A-C

Variant names:

• chr1-206866546-A-C
• NM_018724.4:c.288A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018724.4(IL20):​c.288A>C​(p.Lys96Asn) 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. 12/21 in silico tools predict a benign 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. K96I) has been classified 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: -0.172

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25340325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20	NM_018724.4	c.288A>C	p.Lys96Asn	missense_variant	Exon 4 of 6	ENST00000367098.6	NP_061194.2
IL20	NM_001385166.1	c.288A>C	p.Lys96Asn	missense_variant	Exon 5 of 7		NP_001372095.1
IL20	NM_001385167.1	c.288A>C	p.Lys96Asn	missense_variant	Exon 6 of 8		NP_001372096.1
IL20	NM_001385165.1	c.288A>C	p.Lys96Asn	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.288A>C	p.Lys96Asn	missense_variant	Exon 4 of 6	1	NM_018724.4	ENSP00000356065.1
IL20	ENST00000367096.7	c.288A>C	p.Lys96Asn	missense_variant	Exon 3 of 5	1		ENSP00000356063.3
IL20	ENST00000391930.3	c.288A>C	p.Lys96Asn	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

Sep 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.288A>C (p.K96N) alteration is located in exon 3 (coding exon 3) of the IL20 gene. This alteration results from a A to C substitution at nucleotide position 288, causing the lysine (K) at amino acid position 96 to be replaced by an asparagine (N). 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	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.63	.;T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.090
Sift	Benign	0.086	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.046	B;B;.
Vest4		0.40
MutPred		0.57		Loss of methylation at K96 (P = 0.0011);Loss of methylation at K96 (P = 0.0011);Loss of methylation at K96 (P = 0.0011);
MVP		0.48
MPC		0.17
ClinPred		0.36	T
GERP RS		-4.1
Varity_R		0.33
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-207039891;