3-9906997-G-T

Variant names:

• chr3-9906997-G-T
• rs764951330
• NM_153480.2:c.563G>T

Variant summary

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

The NM_153480.2(IL17RE):​c.563G>T​(p.Arg188Leu) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R188Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RE NM_153480.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• Publications: 1 publications found

Genes affected

IL17RE (HGNC:18439): (interleukin 17 receptor E) This gene encodes a transmembrane protein that functions as the receptor for interleukin-17C. The encoded protein signals to downstream components of the mitogen activated protein kinase (MAPK) pathway. Activity of this protein is important in the immune response to bacterial pathogens. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2013]

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=0.29356474).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153480.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RE	NM_153480.2	MANE Select	c.563G>T	p.Arg188Leu	missense	Exon 6 of 16	NP_705613.1	Q8NFR9-1
	IL17RE	NM_153483.2		c.683G>T	p.Arg228Leu	missense	Exon 7 of 17	NP_705616.2	Q8NFR9
	IL17RE	NM_153481.2		c.215G>T	p.Arg72Leu	missense	Exon 4 of 14	NP_705614.1	Q8NFR9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RE	ENST00000383814.8	TSL:1 MANE Select	c.563G>T	p.Arg188Leu	missense	Exon 6 of 16	ENSP00000373325.3	Q8NFR9-1
	IL17RE	ENST00000421412.5	TSL:1	c.662G>T	p.Arg221Leu	missense	Exon 7 of 17	ENSP00000404916.1	J3KQN7
	IL17RE	ENST00000865435.1		c.329G>T	p.Arg110Leu	missense	Exon 3 of 13	ENSP00000535494.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.87
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.39		Loss of disorder (P = 0.0612)
MVP		0.50
ClinPred		0.96	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.50
Mutation Taster		=83/17	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: rs764951330; hg19: chr3-9948681;