Variant 16-3067997-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001376923.1(IL32):c.128T>C(p.Leu43Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

IL32
NM_001376923.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.709

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1 link	c.128T>C	p.Leu43Pro	missense_variant	Exon 5 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.128T>C	p.Leu43Pro	missense_variant	Exon 5 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

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.128T>C (p.L43P) alteration is located in exon 6 (coding exon 4) of the IL32 gene. This alteration results from a T to C substitution at nucleotide position 128, causing the leucine (L) at amino acid position 43 to be replaced by a proline (P). 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

0.88

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

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

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.42

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

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.44

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

-0.82

MutationAssessor

Benign

0.0

.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;N;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.8

D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;N

REVEL

Uncertain

0.29

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

D;D;T;D;D;T;D;D;D;D;D;D;D;T;D;D;T;D;D;D;D;D;D;D;T;T

Polyphen

0.98

D;P;P;.;D;P;D;D;D;D;D;.;D;.;D;D;.;P;.;D;D;.;P;D;.;.

Vest4

0.43

MutPred

0.68

.;Gain of loop (P = 0.0013);.;.;.;.;.;.;.;.;.;Gain of loop (P = 0.0013);.;.;.;.;.;Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);.;.;.;Gain of loop (P = 0.0013);.;.;.;

MVP

0.66

MPC

0.38

ClinPred

0.62

GERP RS

0.84

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.60

gMVP

0.045

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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