16-3068194-G-C

Variant summary

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

The NM_001376923.1(IL32):ā€‹c.156G>Cā€‹(p.Glu52Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000758 in 1,452,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000076 ( 0 hom. )

Consequence

IL32
NM_001376923.1 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0630
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=0.092404515).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL32NM_001376923.1 linkc.156G>C p.Glu52Asp missense_variant Exon 6 of 7 ENST00000525643.7 NP_001363852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL32ENST00000525643.7 linkc.156G>C p.Glu52Asp missense_variant Exon 6 of 7 1 NM_001376923.1 ENSP00000432218.3 P24001-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000215
AC:
5
AN:
232114
Hom.:
0
AF XY:
0.0000240
AC XY:
3
AN XY:
125200
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000289
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000758
AC:
11
AN:
1452064
Hom.:
0
Cov.:
31
AF XY:
0.00000970
AC XY:
7
AN XY:
721338
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000229
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.156G>C (p.E52D) alteration is located in exon 7 (coding exon 5) of the IL32 gene. This alteration results from a G to C substitution at nucleotide position 156, causing the glutamic acid (E) at amino acid position 52 to be replaced by an aspartic acid (D). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
9.6
DANN
Uncertain
0.99
DEOGEN2
Benign
0.018
.;T;.;.;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;.;T;T;.;.;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.41
.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;T;.;T;T;T;T;T;T;T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.092
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;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.0
.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;.;.;N;.;.;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-2.1
N;N;N;D;N;N;N;D;N;N;N;N;N;N;N;N;N;N;N;N;D;N;N;N;N;N;N
REVEL
Benign
0.066
Sift
Benign
0.16
T;D;T;T;T;T;T;T;T;D;T;T;T;T;T;D;D;T;D;T;T;D;D;T;T;D;T
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;T;T;D;D;D;D;D;D;D;T;T
Polyphen
0.46
P;P;.;P;P;P;P;P;P;.;P;.;P;P;.;P;.;.;.;P;P;.;P;P;.;.;.
Vest4
0.14
MutPred
0.19
.;Loss of helix (P = 0.0376);.;.;.;.;.;.;.;Loss of helix (P = 0.0376);.;.;.;.;.;Loss of helix (P = 0.0376);.;.;Loss of helix (P = 0.0376);.;.;.;Loss of helix (P = 0.0376);.;.;.;.;
MVP
0.59
MPC
0.49
ClinPred
0.078
T
GERP RS
-0.20
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.057
gMVP
0.013

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: rs747208885; hg19: chr16-3118195; API