rs587776980

chr3-57097973-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_017563.5(IL17RD):c.1730C>A(p.Pro577Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RD NM_017563.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.80

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-57097973-G-T is Pathogenic according to our data. Variant chr3-57097973-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 50871.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RD	NM_017563.5	c.1730C>A	p.Pro577Gln	missense_variant	12/13	ENST00000296318.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RD	ENST00000296318.12	c.1730C>A	p.Pro577Gln	missense_variant	12/13	1	NM_017563.5	P1
IL17RD	ENST00000320057.9	c.1298C>A	p.Pro433Gln	missense_variant	13/14	1
IL17RD	ENST00000463523.5	c.1298C>A	p.Pro433Gln	missense_variant	12/13	1
IL17RD	ENST00000469841.5	n.1667C>A		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypogonadotropic hypogonadism 18 with anosmia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 02, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T;.;.;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T;.;.;T
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.8	D;D;D;.
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Uncertain	0.0070	D;D;D;.
Polyphen		0.79	P;.;.;.
Vest4		0.52
MutPred		0.40		Loss of ubiquitination at K581 (P = 0.1166);.;.;.;
MVP		0.43
MPC		0.55
ClinPred		0.86	D
GERP RS		5.6
Varity_R		0.23
gMVP		0.26

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: rs587776980; hg19: chr3-57132001;