3-9920934-G-T

Variant names:

• chr3-9920934-G-T
• rs772677090
• NM_153460.4:c.587G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000403601.8(IL17RC):​c.587G>T​(p.Gly196Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. G196W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IL17RC ENST00000403601.8 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.54
• Publications: 1 publications found

Genes affected

IL17RC (HGNC:18358): (interleukin 17 receptor C) This gene encodes a single-pass type I membrane protein that shares similarity with the interleukin-17 receptor (IL-17RA). Unlike IL-17RA, which is predominantly expressed in hemopoietic cells, and binds with high affinity to only IL-17A, this protein is expressed in nonhemopoietic tissues, and binds both IL-17A and IL-17F with similar affinities. The proinflammatory cytokines, IL-17A and IL-17F, have been implicated in the progression of inflammatory and autoimmune diseases. Multiple alternatively spliced transcript variants encoding different isoforms have been detected for this gene, and it has been proposed that soluble, secreted proteins lacking transmembrane and intracellular domains may function as extracellular antagonists to cytokine signaling. [provided by RefSeq, Feb 2011]

IL17RC Gene-Disease associations (from GenCC):

• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• candidiasis, familial, 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000288550 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27611434).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000403601.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	NM_153460.4	MANE Select	c.587G>T	p.Gly196Val	missense	Exon 7 of 19	NP_703190.2
	IL17RC	NM_153461.4		c.800G>T	p.Gly267Val	missense	Exon 7 of 19	NP_703191.2
	IL17RC	NM_001203263.2		c.587G>T	p.Gly196Val	missense	Exon 7 of 18	NP_001190192.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	ENST00000403601.8	TSL:1 MANE Select	c.587G>T	p.Gly196Val	missense	Exon 7 of 19	ENSP00000384969.3
	IL17RC	ENST00000413608.2	TSL:1	c.587G>T	p.Gly196Val	missense	Exon 7 of 18	ENSP00000396064.1
	IL17RC	ENST00000416074.6	TSL:1	c.587G>T	p.Gly196Val	missense	Exon 7 of 17	ENSP00000395315.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000418 AC: 1 AN: 239138 AF XY: 0.00000772

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000310

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455116 Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3 AN XY: 723726

African (AFR) AF: 0.00 AC: 0 AN: 33114

American (AMR) AF: 0.0000232 AC: 1 AN: 43076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 84714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109962

Other (OTH) AF: 0.0000166 AC: 1 AN: 60068

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Candidiasis, familial, 9 (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.021	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.45		Loss of loop (P = 0.0112)
MVP		0.25
MPC		0.85
ClinPred		0.77	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.44
gMVP		0.40
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs772677090; hg19: chr3-9962618;