Genetic Variant NM_017563.5:c.1403C>G (chr3-57098300-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_017563.5(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. 14/22 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
NM_017563.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.77

Publications

5 publications found

Variant links:

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]

IL17RD Gene-Disease associations (from GenCC):

Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypogonadotropic hypogonadism 18 with or without anosmia
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

IL17RD links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 VariationId is 50870.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.2031819).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017563.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RD	NM_017563.5	MANE Select	c.1403C>G	p.Ser468Trp	missense	Exon 12 of 13	NP_060033.3
	IL17RD	NM_001318864.2		c.971C>G	p.Ser324Trp	missense	Exon 13 of 14	NP_001305793.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL17RD	ENST00000296318.12	TSL:1 MANE Select	c.1403C>G	p.Ser468Trp	missense	Exon 12 of 13	ENSP00000296318.7
IL17RD	ENST00000320057.9	TSL:1	c.971C>G	p.Ser324Trp	missense	Exon 13 of 14	ENSP00000322250.5
IL17RD	ENST00000463523.5	TSL:1	c.971C>G	p.Ser324Trp	missense	Exon 12 of 13	ENSP00000417516.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

0.16

Eigen_PC

Benign

0.053

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

2.8

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.6

REVEL

Benign

0.15

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.53

MVP

0.43

MPC

0.69

ClinPred

0.83

GERP RS

5.0

Varity_R

0.12

gMVP

0.39

Mutation Taster

=32/68

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over