chr16-88639881-A-G

Position:

• chr16-88639881-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013278.4(IL17C):​c.403A>G​(p.Ile135Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL17C NM_013278.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.10

Genes affected

IL17C (HGNC:5983): (interleukin 17C) The protein encoded by this gene is a T cell-derived cytokine that shares the sequence similarity with IL17. This cytokine was reported to stimulate the release of tumor necrosis factor alpha and interleukin 1 beta from a monocytic cell line. The expression of this cytokine was found to be restricted to activated T cells. [provided by RefSeq, Jul 2008]

IL17C (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15013182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17C	NM_013278.4	c.403A>G	p.Ile135Val	missense_variant	3/3	ENST00000244241.5	NP_037410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17C	ENST00000244241.5	c.403A>G	p.Ile135Val	missense_variant	3/3	1	NM_013278.4	ENSP00000244241.4
IL17C	ENST00000569133.1	n.787A>G		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

The c.403A>G (p.I135V) alteration is located in exon 3 (coding exon 3) of the IL17C gene. This alteration results from a A to G substitution at nucleotide position 403, causing the isoleucine (I) at amino acid position 135 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.5
DANN	Benign	0.76
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.044
Sift	Benign	0.26	T
Sift4G	Benign	0.29	T
Polyphen		0.0080	B
Vest4		0.077
MutPred		0.50		Loss of catalytic residue at I135 (P = 0.0604);
MVP		0.48
MPC		0.12
ClinPred		0.45	T
GERP RS		3.5
Varity_R		0.078
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88706289;