Variant 16-3069114-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001376923.1(IL32):c.326T>G(p.Met109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 151,990 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 (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL32
NM_001376923.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11087403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1 link	c.326T>G	p.Met109Arg	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.326T>G	p.Met109Arg	missense_variant	Exon 7 of 7	1	NM_001376923.1	ENSP00000432218.3		P24001-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00107

AC:

1526

AN:

1422818

Hom.:

Cov.:

AF XY:

0.000990

AC XY:

702

AN XY:

709018

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000310

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.000574

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.000847

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.326T>G (p.M109R) alteration is located in exon 8 (coding exon 6) of the IL32 gene. This alteration results from a T to G substitution at nucleotide position 326, causing the methionine (M) at amino acid position 109 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Benign

2.1

DANN

Benign

0.73

DEOGEN2

Benign

0.052

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.46

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

M_CAP

Benign

0.0020

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

-1.1

MutationAssessor

Benign

0.55

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

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.3

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

0.22

Sift

Uncertain

0.0070

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

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

Polyphen

0.010

B;B;B;.;B;B;B;B;B;.;B;.;B;B;.;B;.;.;B;.;B;B;.;.;.;.

Vest4

0.26

MutPred

0.50

.;Gain of MoRF binding (P = 0.0534);.;.;.;.;.;.;.;Gain of MoRF binding (P = 0.0534);.;.;.;.;.;Gain of MoRF binding (P = 0.0534);.;.;.;.;Gain of MoRF binding (P = 0.0534);.;.;.;.;.;

MVP

0.14

MPC

0.34

ClinPred

0.069

GERP RS

-3.8

Varity_R

0.46

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over