1-206866545-A-T

Variant names:

• chr1-206866545-A-T
• rs375942033
• NM_018724.4:c.287A>T

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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K96N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: IL20 NM_018724.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL20	NM_018724.4	c.287A>T	p.Lys96Ile	missense_variant	Exon 4 of 6	ENST00000367098.6	NP_061194.2
IL20	NM_001385166.1	c.287A>T	p.Lys96Ile	missense_variant	Exon 5 of 7		NP_001372095.1
IL20	NM_001385167.1	c.287A>T	p.Lys96Ile	missense_variant	Exon 6 of 8		NP_001372096.1
IL20	NM_001385165.1	c.287A>T	p.Lys96Ile	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.287A>T	p.Lys96Ile	missense_variant	Exon 4 of 6	1	NM_018724.4	ENSP00000356065.1
IL20	ENST00000367096.7	c.287A>T	p.Lys96Ile	missense_variant	Exon 3 of 5	1		ENSP00000356063.3
IL20	ENST00000391930.3	c.287A>T	p.Lys96Ile	missense_variant	Exon 3 of 4	1		ENSP00000375796.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461840 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727230

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.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.76	.;T;T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.1	M;M;M
PrimateAI	Benign	0.40	T
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	D
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

Other links and lift over

dbSNP: rs375942033; hg19: chr1-207039890;