14-23373272-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022789.4(IL25):​c.154C>A​(p.Leu52Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IL25
NM_022789.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.590
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18792433).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL25NM_172314.2 linkuse as main transcriptc.106C>A p.Leu36Met missense_variant 2/3 ENST00000397242.3 NP_758525.1
IL25NM_022789.4 linkuse as main transcriptc.154C>A p.Leu52Met missense_variant 1/2 NP_073626.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL25ENST00000397242.3 linkuse as main transcriptc.106C>A p.Leu36Met missense_variant 2/31 NM_172314.2 ENSP00000380417 P2Q9H293-2
IL25ENST00000329715.2 linkuse as main transcriptc.154C>A p.Leu52Met missense_variant 1/21 ENSP00000328111 A2Q9H293-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461868
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 14, 2024The c.154C>A (p.L52M) alteration is located in exon 1 (coding exon 1) of the IL25 gene. This alteration results from a C to A substitution at nucleotide position 154, causing the leucine (L) at amino acid position 52 to be replaced by a methionine (M). 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
0.15
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
.;T
Eigen
Benign
-0.095
Eigen_PC
Benign
-0.093
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.35
T;T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.0
.;M
MutationTaster
Benign
0.92
N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.79
N;N
REVEL
Benign
0.080
Sift
Benign
0.037
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.32
B;D
Vest4
0.26
MutPred
0.48
.;Loss of catalytic residue at L52 (P = 0.0052);
MVP
0.66
MPC
0.44
ClinPred
0.51
D
GERP RS
2.7
Varity_R
0.12
gMVP
0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23842481; API