chr5-135892431-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000590.2(IL9):​c.395T>A​(p.Phe132Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,258 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

IL9
NM_000590.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14
Variant links:
Genes affected
IL9 (HGNC:6029): (interleukin 9) The protein encoded by this gene is a cytokine that acts as a regulator of a variety of hematopoietic cells. This cytokine stimulates cell proliferation and prevents apoptosis. It functions through the interleukin 9 receptor (IL9R), which activates different signal transducer and activator (STAT) proteins and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for asthma. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of bronchial hyperresponsiveness. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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
IL9NM_000590.2 linkuse as main transcriptc.395T>A p.Phe132Tyr missense_variant 5/5 ENST00000274520.2 NP_000581.1
LOC124901074XR_007058947.1 linkuse as main transcriptn.347-11A>T splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL9ENST00000274520.2 linkuse as main transcriptc.395T>A p.Phe132Tyr missense_variant 5/51 NM_000590.2 ENSP00000274520 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1460258
Hom.:
0
Cov.:
29
AF XY:
0.0000124
AC XY:
9
AN XY:
726408
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000144
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 GeneticsDec 01, 2022The c.395T>A (p.F132Y) alteration is located in exon 5 (coding exon 5) of the IL9 gene. This alteration results from a T to A substitution at nucleotide position 395, causing the phenylalanine (F) at amino acid position 132 to be replaced by a tyrosine (Y). 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
0.29
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.52
D
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
0.93
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.26
Sift
Benign
0.049
D
Sift4G
Uncertain
0.052
T
Polyphen
1.0
D
Vest4
0.39
MutPred
0.70
Loss of methylation at K134 (P = 0.0587);
MVP
0.66
MPC
0.84
ClinPred
0.90
D
GERP RS
5.5
Varity_R
0.17
gMVP
0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1762882770; hg19: chr5-135228120; API