16-3069090-G-T

Variant names:

• chr16-3069090-G-T
• rs764366058
• NM_001376923.1:c.302G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001376923.1(IL32):​c.302G>T​(p.Gly101Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000069 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IL32 NM_001376923.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.40

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044130802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL32	NM_001376923.1	c.302G>T	p.Gly101Val	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	c.302G>T	p.Gly101Val	missense_variant	Exon 7 of 7	1	NM_001376923.1	ENSP00000432218.3

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152154 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000222 AC: 5 AN: 225690 Hom.: 0 AF XY: 0.0000243 AC XY: 3 AN XY: 123520

Gnomad AFR exome AF: 0.000242

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000199

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000687 AC: 10 AN: 1456658 Hom.: 0 Cov.: 53 AF XY: 0.00000828 AC XY: 6 AN XY: 724214

Gnomad4 AFR exome AF: 0.000211

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000525 AC: 8 AN: 152272 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74472

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000167 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302G>T (p.G101V) alteration is located in exon 8 (coding exon 6) of the IL32 gene. This alteration results from a G to T substitution at nucleotide position 302, causing the glycine (G) at amino acid position 101 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.50
DANN	Benign	0.54
DEOGEN2	Benign	0.041	.;T;T;.;.;T;.;.;.;.;.;T;.;.;.;.;.;T;.;.;.;.;T;T;.;.;T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.58	.;.;T;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;.;T;T;T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.044	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	-1.0	T
MutationAssessor	Benign	0.34	.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;.;N;.;.;.;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N;D;.;D;N;D;N;N;N;N;N;D;N;D;N;N;D;D;D;N;N;N;D;D;N;D;D;N;D
REVEL	Benign	0.18
Sift	Benign	0.10	T;D;.;T;D;T;T;T;T;D;T;T;T;T;T;T;T;D;T;T;T;D;T;D;T;T;D;T;T
Sift4G	Benign	0.23	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		0.021	B;B;B;.;B;B;B;B;B;B;B;.;B;.;B;B;.;B;.;.;B;B;.;B;B;.;.;.;.
Vest4		0.13
MutPred		0.20		.;Loss of loop (P = 0.0022);.;.;.;.;.;.;.;.;.;Loss of loop (P = 0.0022);.;.;.;.;.;Loss of loop (P = 0.0022);.;.;.;.;.;Loss of loop (P = 0.0022);.;.;.;.;.;
MVP		0.42
MPC		0.48
ClinPred		0.012	T
GERP RS		-3.8
Varity_R		0.059
gMVP		0.0096

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

LitVar

Other links and lift over

dbSNP: rs764366058; hg19: chr16-3119091;