Variant 16-3069086-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001376923.1(IL32):c.298C>A(p.Pro100Thr) 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.554

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]

IL32 links:

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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=0.08682406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1 link	c.298C>A	p.Pro100Thr	missense_variant	Exon 7 of 7	ENST00000525643.7	NP_001363852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL32	ENST00000525643.7 link	c.298C>A	p.Pro100Thr	missense_variant	Exon 7 of 7	1	NM_001376923.1	ENSP00000432218.3		P24001-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298C>A (p.P100T) alteration is located in exon 8 (coding exon 6) of the IL32 gene. This alteration results from a C to A substitution at nucleotide position 298, causing the proline (P) at amino acid position 100 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

.;T;T;.;.;T;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;T;T;.;.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.63

.;.;T;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;.;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.087

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

-0.95

MutationAssessor

Benign

0.81

.;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;L;.;.;.;.;.;L;.;.;.;.;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-4.2

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;D;D;D

REVEL

Benign

0.071

Sift

Benign

0.24

T;D;.;T;D;D;T;T;T;D;T;D;T;D;T;T;D;D;D;D;T;D;D;D;T;D;D;D;D

Sift4G

Pathogenic

0.0

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;D;D;D;D

Polyphen

0.46

P;B;B;.;P;B;P;P;P;P;P;.;P;.;P;P;.;B;.;.;P;P;.;B;P;.;.;.;.

Vest4

0.28

MutPred

0.24

.;Gain of helix (P = 0.0093);.;.;.;.;.;.;.;.;.;Gain of helix (P = 0.0093);.;.;.;.;.;Gain of helix (P = 0.0093);.;.;.;.;.;Gain of helix (P = 0.0093);.;.;.;.;.;

MVP

0.31

MPC

0.56

ClinPred

0.26

GERP RS

-3.4

Varity_R

0.26

gMVP

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over