chr6-52187718-A-T

Position:

• chr6-52187718-A-T

Variant summary

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

The NM_002190.3(IL17A):​c.143A>T​(p.Asn48Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17A NM_002190.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30

Genes affected

IL17A (HGNC:5981): (interleukin 17A) This gene is a member of the IL-17 receptor family which includes five members (IL-17RA-E) and the encoded protein is a proinflammatory cytokine produced by activated T cells. IL-17A-mediated downstream pathways induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins. The encoded protein elicits crucial impacts on host defense, cell trafficking, immune modulation, and tissue repair, with a key role in the induction of innate immune defenses. This cytokine stimulates non-hematopoietic cells and promotes chemokine production thereby attracting myeloid cells to inflammatory sites. This cytokine also regulates the activities of NF-kappaB and mitogen-activated protein kinases and can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). IL-17A plays a pivotal role in various infectious diseases, inflammatory and autoimmune disorders, and cancer. High levels of this cytokine are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis. The lung damage induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL17A. [provided by RefSeq, Sep 2020]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17A	NM_002190.3	c.143A>T	p.Asn48Ile	missense_variant	2/3	ENST00000648244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17A	ENST00000648244.1	c.143A>T	p.Asn48Ile	missense_variant	2/3		NM_002190.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 03, 2023

The c.143A>T (p.N48I) alteration is located in exon 2 (coding exon 2) of the IL17A gene. This alteration results from a A to T substitution at nucleotide position 143, causing the asparagine (N) at amino acid position 48 to be replaced by an isoleucine (I). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.86	D;D
Eigen	Benign	0.15
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	0.93	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.3	.;D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	.;D
Sift4G	Benign	0.16	.;T
Polyphen		0.99	D;D
Vest4		0.75
MutPred		0.53		Loss of disorder (P = 0.0169);Loss of disorder (P = 0.0169);
MVP		0.77
MPC		0.87
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.71
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: chr6-52052516;