rs1177739539

Variant names:

• chr16-3068223-A-C
• rs1177739539
• NM_001376923.1:c.185A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-3068223-A-C
• chr16-3068223-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376923.1(IL32):​c.185A>C​(p.Tyr62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IL32 NM_001376923.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12906012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376923.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL32	NM_001376923.1	MANE Select	c.185A>C	p.Tyr62Ser	missense	Exon 6 of 7	NP_001363852.1	P24001-2
	IL32	NM_001308078.4		c.323A>C	p.Tyr108Ser	missense	Exon 5 of 6	NP_001295007.1	P24001-1
	IL32	NM_001369587.3		c.323A>C	p.Tyr108Ser	missense	Exon 5 of 6	NP_001356516.1	P24001-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL32	ENST00000525643.7	TSL:1 MANE Select	c.185A>C	p.Tyr62Ser	missense	Exon 6 of 7	ENSP00000432218.3	P24001-2
	IL32	ENST00000396890.6	TSL:1	c.323A>C	p.Tyr108Ser	missense	Exon 5 of 6	ENSP00000380099.2	P24001-1
	IL32	ENST00000325568.9	TSL:1	c.185A>C	p.Tyr62Ser	missense	Exon 6 of 7	ENSP00000324742.5	P24001-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000450 AC: 1 AN: 222402 AF XY: 0.00000834

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446548 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718138

African (AFR) AF: 0.00 AC: 0 AN: 33218

American (AMR) AF: 0.00 AC: 0 AN: 42278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 39116

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104524

Other (OTH) AF: 0.00 AC: 0 AN: 59768

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	1.0
DANN	Benign	0.75
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Benign	0.40	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.40
MutPred		0.42		Gain of disorder (P = 0.0096)
MVP		0.53
MPC		0.50
ClinPred		0.28	T
GERP RS		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.014

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

Other links and lift over

dbSNP: rs1177739539; hg19: chr16-3118224;