3-57096488-C-T

Variant names:

• chr3-57096488-C-T
• NM_017563.5:c.2125G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017563.5(IL17RD):​c.2125G>A​(p.Ala709Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RD NM_017563.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.148

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037386835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RD	NM_017563.5	c.2125G>A	p.Ala709Thr	missense_variant	Exon 13 of 13	ENST00000296318.12	NP_060033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RD	ENST00000296318.12	c.2125G>A	p.Ala709Thr	missense_variant	Exon 13 of 13	1	NM_017563.5	ENSP00000296318.7
IL17RD	ENST00000320057.9	c.1693G>A	p.Ala565Thr	missense_variant	Exon 14 of 14	1		ENSP00000322250.5
IL17RD	ENST00000463523.5	c.1693G>A	p.Ala565Thr	missense_variant	Exon 13 of 13	1		ENSP00000417516.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2125G>A (p.A709T) alteration is located in exon 13 (coding exon 13) of the IL17RD gene. This alteration results from a G to A substitution at nucleotide position 2125, causing the alanine (A) at amino acid position 709 to be replaced by a threonine (T). 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	0.065
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.061	T;.;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.61	T;.;.;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.14	N;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.52	N;N;N;.
REVEL	Benign	0.19
Sift	Benign	0.40	T;T;T;.
Sift4G	Benign	0.44	T;T;T;.
Polyphen		0.0	B;.;.;.
Vest4		0.018
MutPred		0.050		Loss of glycosylation at P708 (P = 0.0155);.;.;.;
MVP		0.19
MPC		0.12
ClinPred		0.28	T
GERP RS		2.9
Varity_R		0.026
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr3-57130516;