chr3-159989073-C-T

Variant names:

• chr3-159989073-C-T
• ENST00000305579.7:c.17C>T

Variant summary

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

The NM_000882.4(IL12A):​c.17C>T​(p.Ser6Leu) 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. 13/19 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)
• Consequence: IL12A NM_000882.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.960
• Publications: 0 publications found

Genes affected

IL12A (HGNC:5969): (interleukin 12A) This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]

IL12A-AS1 (HGNC:49094): (IL12A antisense RNA 1)

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=0.06988415).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000882.4. 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
	IL12A	NM_001397992.1	MANE Select	c.-86C>T		5_prime_UTR	Exon 1 of 7	NP_001384921.1	P29459
	IL12A	NM_000882.4		c.17C>T	p.Ser6Leu	missense	Exon 1 of 7	NP_000873.2
	IL12A	NM_001354582.2		c.17C>T	p.Ser6Leu	missense	Exon 1 of 6	NP_001341511.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12A	ENST00000305579.7	TSL:1	c.17C>T	p.Ser6Leu	missense	Exon 1 of 7	ENSP00000303231.2	O60595
	IL12A	ENST00000699704.1	MANE Select	c.-86C>T		5_prime_UTR	Exon 1 of 7	ENSP00000514529.1	P29459
	IL12A	ENST00000466512.1	TSL:3	c.-86C>T		5_prime_UTR	Exon 1 of 6	ENSP00000419046.2	E9PGR3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Benign	0.18
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.96
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.071
Sift	Benign	0.19	T
Sift4G	Benign	0.13	T
Polyphen		0.0060	B
Vest4		0.062
MutPred		0.19		Loss of glycosylation at S6 (P = 0.0042)
MVP		0.17
MPC		0.30
ClinPred		0.23	T
GERP RS		3.3
PromoterAI		-0.081	Neutral
gMVP		0.13
Mutation Taster		=94/6	polymorphism

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

hg19: chr3-159706860;