chr3-57097670-A-T

Position:

• chr3-57097670-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017563.5(IL17RD):​c.2033T>A​(p.Leu678Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 6.87

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31243467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RD	NM_017563.5	c.2033T>A	p.Leu678Gln	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.2033T>A	p.Leu678Gln	missense_variant	12/13	1	NM_017563.5	ENSP00000296318	P1
IL17RD	ENST00000320057.9	c.1601T>A	p.Leu534Gln	missense_variant	13/14	1		ENSP00000322250
IL17RD	ENST00000463523.5	c.1601T>A	p.Leu534Gln	missense_variant	12/13	1		ENSP00000417516
IL17RD	ENST00000469841.5	n.1970T>A		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 07, 2024

The c.2033T>A (p.L678Q) alteration is located in exon 12 (coding exon 12) of the IL17RD gene. This alteration results from a T to A substitution at nucleotide position 2033, causing the leucine (L) at amino acid position 678 to be replaced by a glutamine (Q). 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	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T;.;.;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.;.
MutationTaster	Benign	0.92	N;N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.3	N;N;N;.
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		0.80	P;.;.;.
Vest4		0.90
MutPred		0.13		Gain of glycosylation at S675 (P = 0.0201);.;.;.;
MVP		0.43
MPC		0.57
ClinPred		0.89	D
GERP RS		5.9
Varity_R		0.38
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-57131698;