16-3068996-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001376923.1(IL32):​c.208A>G​(p.Thr70Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 34)

Consequence

IL32
NM_001376923.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.81
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.051379174).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL32NM_001376923.1 linkc.208A>G p.Thr70Ala missense_variant Exon 7 of 7 ENST00000525643.7 NP_001363852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL32ENST00000525643.7 linkc.208A>G p.Thr70Ala missense_variant Exon 7 of 7 1 NM_001376923.1 ENSP00000432218.3 P24001-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 31, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.208A>G (p.T70A) alteration is located in exon 8 (coding exon 6) of the IL32 gene. This alteration results from a A to G substitution at nucleotide position 208, causing the threonine (T) at amino acid position 70 to be replaced by an alanine (A). 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
0.19
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.041
DANN
Benign
0.39
DEOGEN2
Benign
0.014
.;T;T;.;.;T;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;T;T;.;.;T;.;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.00085
N
LIST_S2
Benign
0.46
.;.;T;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;.;T;T;T;T;T;T;T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.051
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;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;.;N;.;.;.;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.1
N;N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.034
Sift
Benign
0.32
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;T
Sift4G
Benign
0.51
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;T;T
Polyphen
0.0010
B;B;B;.;P;B;B;B;B;P;B;.;B;.;B;B;.;B;.;.;B;P;.;B;B;.;.;.;.
Vest4
0.025
MutPred
0.13
.;Gain of helix (P = 0.0225);.;.;.;.;.;.;.;.;.;Gain of helix (P = 0.0225);.;.;.;.;.;Gain of helix (P = 0.0225);.;.;.;.;.;Gain of helix (P = 0.0225);.;.;.;.;.;
MVP
0.25
MPC
0.10
ClinPred
0.054
T
GERP RS
-3.4
Varity_R
0.11
gMVP
0.0061

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr16-3118997; API