chr3-9933540-C-G

Variant names:

• chr3-9933540-C-G
• rs1036868156
• NM_153460.4:c.2110C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000403601.8(IL17RC):​c.2110C>G​(p.Pro704Ala) 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. 16/22 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. P704R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL17RC ENST00000403601.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0190
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06950307).

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.2110C>G	p.Pro704Ala	missense	Exon 19 of 19	NP_703190.2
	IL17RC	NM_153461.4		c.2323C>G	p.Pro775Ala	missense	Exon 19 of 19	NP_703191.2
	IL17RC	NM_001203263.2		c.2071C>G	p.Pro691Ala	missense	Exon 18 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.2110C>G	p.Pro704Ala	missense	Exon 19 of 19	ENSP00000384969.3
	IL17RC	ENST00000413608.2	TSL:1	c.2071C>G	p.Pro691Ala	missense	Exon 18 of 18	ENSP00000396064.1
	IL17RC	ENST00000383812.9	TSL:1	c.2065C>G	p.Pro689Ala	missense	Exon 18 of 18	ENSP00000373323.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Candidiasis, familial, 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.1
DANN	Benign	0.65
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.019
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.058
Sift	Benign	0.31	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.12		Loss of glycosylation at P770 (P = 0.0122)
MVP		0.067
MPC		0.23
ClinPred		0.21	T
GERP RS		-0.35
PromoterAI		0.015	Neutral
Varity_R		0.030
gMVP		0.33
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1036868156; hg19: chr3-9975224;