chr14-23375671-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_022789.4(IL25):c.325C>T(p.Arg109Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
IL25
NM_022789.4 missense
NM_022789.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 0.849
Genes affected
IL25 (HGNC:13765): (interleukin 25) The protein encoded by this gene is a cytokine that shares sequence similarity with interleukin 17. This cytokine can induce NF-kappaB activation, and stimulate the production of interleukin 8. Both this cytokine and interleukin 17B are ligands for the cytokine receptor IL17BR. Studies of a similar gene in mice suggest that this cytokine may be a pro-inflammatory cytokine favoring the Th2-type immune response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL25 | NM_172314.2 | c.277C>T | p.Arg93Cys | missense_variant | 3/3 | ENST00000397242.3 | NP_758525.1 | |
IL25 | NM_022789.4 | c.325C>T | p.Arg109Cys | missense_variant | 2/2 | NP_073626.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL25 | ENST00000397242.3 | c.277C>T | p.Arg93Cys | missense_variant | 3/3 | 1 | NM_172314.2 | ENSP00000380417 | P2 | |
IL25 | ENST00000329715.2 | c.325C>T | p.Arg109Cys | missense_variant | 2/2 | 1 | ENSP00000328111 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250828Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135600
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727246
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2023 | The c.325C>T (p.R109C) alteration is located in exon 2 (coding exon 2) of the IL25 gene. This alteration results from a C to T substitution at nucleotide position 325, causing the arginine (R) at amino acid position 109 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;P
Vest4
MutPred
0.68
.;Loss of disorder (P = 0.1236);
MVP
MPC
0.53
ClinPred
D
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