16-3068996-A-G

Variant names:

• chr16-3068996-A-G
• NM_001376923.1:c.208A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.81

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 -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
IL32	NM_001376923.1	c.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
IL32	ENST00000525643.7	c.208A>G	p.Thr70Ala	missense_variant	Exon 7 of 7	1	NM_001376923.1	ENSP00000432218.3

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

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;