Genetic Variant NM_014432.4:c.836T>A (chr6-137004649-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_014432.4(IL20RA):c.836T>A(p.Val279Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IL20RA
NM_014432.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.92

Variant links:

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]

IL20RA links:

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ACMG classification

Classification made for transcript

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
IL20RA	NM_014432.4 link	c.836T>A	p.Val279Asp	missense_variant	Exon 6 of 7	ENST00000316649.10	NP_055247.4	Q9UHF4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL20RA	ENST00000316649.10 link	c.836T>A	p.Val279Asp	missense_variant	Exon 6 of 7	1	NM_014432.4	ENSP00000314976.5	Q9UHF4-1
IL20RA	ENST00000367748.4 link	c.503T>A	p.Val168Asp	missense_variant	Exon 5 of 6	1		ENSP00000356722.1	Q9UHF4-2
IL20RA	ENST00000541547.5 link	c.689T>A	p.Val230Asp	missense_variant	Exon 6 of 7	2		ENSP00000437843.1	Q9UHF4-3
IL20RA	ENST00000468393.5 link	c.503T>A	p.Val168Asp	missense_variant	Exon 5 of 5	4		ENSP00000489177.1	A0A0U1RQU9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727144

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

.;T;.;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.1

.;M;.;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.9

D;D;D;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0090

D;D;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.56

MutPred

0.59

.;Gain of disorder (P = 0.0036);.;.;

MVP

0.84

MPC

1.2

ClinPred

0.92

GERP RS

5.3

Varity_R

0.38

gMVP

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over