chr16-88639926-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013278.4(IL17C):​c.448C>T​(p.Arg150Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,610,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

IL17C
NM_013278.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.372
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18683633).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL17CNM_013278.4 linkuse as main transcriptc.448C>T p.Arg150Trp missense_variant 3/3 ENST00000244241.5 NP_037410.1 Q9P0M4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL17CENST00000244241.5 linkuse as main transcriptc.448C>T p.Arg150Trp missense_variant 3/31 NM_013278.4 ENSP00000244241.4 Q9P0M4
IL17CENST00000569133.1 linkuse as main transcriptn.832C>T non_coding_transcript_exon_variant 2/21

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000331
AC:
8
AN:
241666
Hom.:
0
AF XY:
0.0000453
AC XY:
6
AN XY:
132388
show subpopulations
Gnomad AFR exome
AF:
0.0000676
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000203
Gnomad EAS exome
AF:
0.000113
Gnomad SAS exome
AF:
0.0000656
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000922
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000213
AC:
31
AN:
1457980
Hom.:
0
Cov.:
31
AF XY:
0.0000276
AC XY:
20
AN XY:
725370
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000422
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.0000415
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 27, 2023The c.448C>T (p.R150W) alteration is located in exon 3 (coding exon 3) of the IL17C gene. This alteration results from a C to T substitution at nucleotide position 448, causing the arginine (R) at amino acid position 150 to be replaced by a tryptophan (W). 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
0.13
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.80
T
M_CAP
Uncertain
0.092
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.14
Sift
Benign
0.039
D
Sift4G
Benign
0.065
T
Polyphen
0.93
P
Vest4
0.17
MVP
0.60
MPC
0.39
ClinPred
0.092
T
GERP RS
2.3
Varity_R
0.040
gMVP
0.60

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs371134109; hg19: chr16-88706334; COSMIC: COSV99733305; COSMIC: COSV99733305; API