3-9917335-T-C

Variant names:

• chr3-9917335-T-C
• rs2125112075
• NM_153460.4:c.20T>C

Variant summary

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

The NM_153460.4(IL17RC):​c.20T>C​(p.Leu7Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L7L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 0 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 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
IL17RC	NM_153460.4	c.20T>C	p.Leu7Ser	missense_variant	Exon 1 of 19	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8	c.20T>C	p.Leu7Ser	missense_variant	Exon 1 of 19	1	NM_153460.4	ENSP00000384969.3
ENSG00000288550	ENST00000683484.1	n.20T>C		non_coding_transcript_exon_variant	Exon 1 of 24			ENSP00000507040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Candidiasis, familial, 9 Uncertain:1

Jun 07, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 7 of the IL17RC protein (p.Leu7Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant has not been reported in the literature in individuals with IL17RC-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;.;.;T;.;.;.;.;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.82	T;.;T;T;T;T;T;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.2	M;M;.;M;M;.;M;M;M
PhyloP100		3.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	.;D;D;D;.;D;D;D;D
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	.;D;D;D;.;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;.;D;D;D;D
Polyphen		1.0, 0.99, 1.0	.;D;.;D;D;.;D;.;.
Vest4		0.74
MutPred		0.60		Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);Gain of disorder (P = 0.0091);
MVP		0.59
MPC		0.70
ClinPred		0.99	D
GERP RS		5.3
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.58
gMVP		0.55
Mutation Taster		=70/30	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: rs2125112075; hg19: chr3-9959019;