3-57097694-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_017563.5(IL17RD):c.2009C>T(p.Pro670Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,605,802 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00087 ( 2 hom. )
Consequence
IL17RD
NM_017563.5 missense
NM_017563.5 missense
Scores
7
3
9
Clinical Significance
Conservation
PhyloP100: 7.52
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.10057995).
BS2
High AC in GnomAd4 at 93 AD,Digenic gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL17RD | NM_017563.5 | c.2009C>T | p.Pro670Leu | missense_variant | 12/13 | ENST00000296318.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL17RD | ENST00000296318.12 | c.2009C>T | p.Pro670Leu | missense_variant | 12/13 | 1 | NM_017563.5 | P1 | |
IL17RD | ENST00000320057.9 | c.1577C>T | p.Pro526Leu | missense_variant | 13/14 | 1 | |||
IL17RD | ENST00000463523.5 | c.1577C>T | p.Pro526Leu | missense_variant | 12/13 | 1 | |||
IL17RD | ENST00000469841.5 | n.1946C>T | non_coding_transcript_exon_variant | 12/12 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000611 AC: 93AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000581 AC: 138AN: 237340Hom.: 0 AF XY: 0.000569 AC XY: 73AN XY: 128322
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GnomAD4 exome AF: 0.000868 AC: 1262AN: 1453492Hom.: 2 Cov.: 32 AF XY: 0.000838 AC XY: 605AN XY: 722160
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GnomAD4 genome AF: 0.000611 AC: 93AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41AN XY: 74472
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Identified in the heterozygous state in an individual in published literature, however they were clinically unaffected (PMID: 23643382); This variant is associated with the following publications: (PMID: 23643382) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 06, 2023 | This variant is present in population databases (rs143119752, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 670 of the IL17RD protein (p.Pro670Leu). This variant has not been reported in the literature in individuals affected with IL17RD-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IL17RD protein function. ClinVar contains an entry for this variant (Variation ID: 1442770). - |
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2023 | The c.2009C>T (p.P670L) alteration is located in exon 12 (coding exon 12) of the IL17RD gene. This alteration results from a C to T substitution at nucleotide position 2009, causing the proline (P) at amino acid position 670 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Uncertain
D;D;D;.
Sift4G
Pathogenic
D;D;D;.
Polyphen
D;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at