16-3068006-T-G

Variant summary

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

The NM_001376923.1(IL32):ā€‹c.137T>Gā€‹(p.Leu46Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

IL32
NM_001376923.1 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0750
Variant links:
Genes affected
IL32 (HGNC:16830): (interleukin 32) This gene encodes a member of the cytokine family. The protein contains a tyrosine sulfation site, 3 potential N-myristoylation sites, multiple putative phosphorylation sites, and an RGD cell-attachment sequence. Expression of this protein is increased after the activation of T-cells by mitogens or the activation of NK cells by IL-2. This protein induces the production of TNFalpha from macrophage cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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=0.11005297).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL32NM_001376923.1 linkc.137T>G p.Leu46Arg missense_variant Exon 5 of 7 ENST00000525643.7 NP_001363852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL32ENST00000525643.7 linkc.137T>G p.Leu46Arg missense_variant Exon 5 of 7 1 NM_001376923.1 ENSP00000432218.3 P24001-2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251372
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461832
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000157
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:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.137T>G (p.L46R) alteration is located in exon 6 (coding exon 4) of the IL32 gene. This alteration results from a T to G substitution at nucleotide position 137, causing the leucine (L) at amino acid position 46 to be replaced by an arginine (R). 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
0.76
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.045
.;T;T;.;.;T;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;T;T;.;.;.
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.30
.;.;T;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;T;T;T;T;T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.11
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.0
.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;N;.;.;.
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-3.0
D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.014
D;D;.;D;D;D;D;D;D;D;D;D;D;T;D;D;T;D;D;D;D;D;D;D;T;T
Sift4G
Pathogenic
0.0
D;D;T;T;D;T;D;D;D;D;D;D;D;T;D;D;T;D;D;D;D;T;D;D;T;T
Polyphen
1.0
D;D;D;.;D;D;D;D;D;D;D;.;D;.;D;D;.;D;.;D;D;.;D;D;.;.
Vest4
0.44
MutPred
0.38
.;Loss of helix (P = 0.0138);.;.;.;.;.;.;.;.;.;Loss of helix (P = 0.0138);.;.;.;.;.;Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);.;.;.;Loss of helix (P = 0.0138);.;.;.;
MVP
0.82
MPC
0.40
ClinPred
0.27
T
GERP RS
0.78
Varity_R
0.36
gMVP
0.014

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs774367638; hg19: chr16-3118007; API