16-3067997-T-C

Variant names:

• chr16-3067997-T-C
• NM_001376923.1:c.128T>C

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.709

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 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	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	c.128T>C	p.Leu43Pro	missense_variant	Exon 5 of 7	1	NM_001376923.1	ENSP00000432218.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	16
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	N
LIST_S2	Benign	0.42	.;.;T;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;T;T;T;T;T;T
M_CAP	Benign	0.019	T
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	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;N;.;.;.
PrimateAI	Uncertain	0.51	T
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	D
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.

Other links and lift over

hg19: chr16-3117998;