chr6-137001686-G-A

Position:

• chr6-137001686-G-A

Variant summary

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

The NM_014432.4(IL20RA):​c.1534C>T​(p.Leu512Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL20RA NM_014432.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946

Genes affected

IL20RA (HGNC:6003): (interleukin 20 receptor subunit alpha) This gene encodes a member of the type II cytokine receptor family. The encoded protein is a subunit of the receptor for interleukin 20, a cytokine that may be involved in epidermal function. The interleukin 20 receptor is a heterodimeric complex consisting of the encoded protein and interleukin 20 receptor beta. This gene and interleukin 20 receptor beta are highly expressed in skin, and are upregulated in psoriasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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=0.0843606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL20RA	NM_014432.4	c.1534C>T	p.Leu512Phe	missense_variant	7/7	ENST00000316649.10	NP_055247.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL20RA	ENST00000316649.10	c.1534C>T	p.Leu512Phe	missense_variant	7/7	1	NM_014432.4	ENSP00000314976.5
IL20RA	ENST00000367748.4	c.1201C>T	p.Leu401Phe	missense_variant	6/6	1		ENSP00000356722.1
IL20RA	ENST00000541547.5	c.1387C>T	p.Leu463Phe	missense_variant	7/7	2		ENSP00000437843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

The c.1534C>T (p.L512F) alteration is located in exon 7 (coding exon 7) of the IL20RA gene. This alteration results from a C to T substitution at nucleotide position 1534, causing the leucine (L) at amino acid position 512 to be replaced by a phenylalanine (F). 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	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.5
DANN	Benign	0.51
DEOGEN2	Benign	0.0097	.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.084	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.23	T;T;T
Sift4G	Benign	0.94	T;T;T
Polyphen		0.013, 0.0040	.;B;B
Vest4		0.057
MutPred		0.18		.;Gain of sheet (P = 0.0166);.;
MVP		0.72
MPC		0.29
ClinPred		0.15	T
GERP RS		1.6
Varity_R		0.038
gMVP		0.11

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: chr6-137322823;