chr16-88639867-T-C

Position:

• chr16-88639867-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_013278.4(IL17C):​c.389T>C​(p.Leu130Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,449,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IL17C NM_013278.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17C	NM_013278.4	c.389T>C	p.Leu130Pro	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.389T>C	p.Leu130Pro	missense_variant	3/3	1	NM_013278.4	ENSP00000244241.4
IL17C	ENST00000569133.1	n.773T>C		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449966 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

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

Jun 06, 2023

The c.389T>C (p.L130P) alteration is located in exon 3 (coding exon 3) of the IL17C gene. This alteration results from a T to C substitution at nucleotide position 389, causing the leucine (L) at amino acid position 130 to be replaced by a proline (P). 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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	-0.053	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.59
MutPred		0.90		Loss of helix (P = 0.028);
MVP		0.86
MPC		0.65
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.65
gMVP		0.82

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

LitVar

Other links and lift over

dbSNP: rs1479154375; hg19: chr16-88706275;