3-57098300-G-C

Position:

• chr3-57098300-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The ENST00000296318.12(IL17RD):​c.1403C>G​(p.Ser468Trp) 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. 13/21 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. S468L) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RD ENST00000296318.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

Genes affected

IL17RD (HGNC:17616): (interleukin 17 receptor D) This gene encodes a membrane protein belonging to the interleukin-17 receptor (IL-17R) protein family. The encoded protein is a component of the interleukin-17 receptor signaling complex, and the interaction between this protein and IL-17R does not require the interleukin. The gene product also affects fibroblast growth factor signaling, inhibiting or stimulating growth through MAPK/ERK signaling. Alternate splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr3-57098300-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 50870.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.2031819).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RD	NM_017563.5	c.1403C>G	p.Ser468Trp	missense_variant	12/13	ENST00000296318.12	NP_060033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RD	ENST00000296318.12	c.1403C>G	p.Ser468Trp	missense_variant	12/13	1	NM_017563.5	ENSP00000296318	P1
IL17RD	ENST00000320057.9	c.971C>G	p.Ser324Trp	missense_variant	13/14	1		ENSP00000322250
IL17RD	ENST00000463523.5	c.971C>G	p.Ser324Trp	missense_variant	12/13	1		ENSP00000417516
IL17RD	ENST00000469841.5	n.1340C>G		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.;.;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.87	D;.;.;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.;.
MutationTaster	Benign	0.86	N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	N;N;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;D;D;.
Sift4G	Uncertain	0.0040	D;D;D;.
Polyphen		0.99	D;.;.;.
Vest4		0.53
MVP		0.43
MPC		0.69
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.39

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: rs145221454; hg19: chr3-57132328;