12-68225228-C-T

Variant names:

• chr12-68225228-C-T
• rs767404352
• NM_018402.2:c.284G>A

Variant summary

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

The NM_018402.2(IL26):​c.284G>A​(p.Gly95Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G95A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL26 NM_018402.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• Publications: 0 publications found

Genes affected

IL26 (HGNC:17119): (interleukin 26) This gene was identified by its overexpression specifically in herpesvirus samimiri-transformed T cells. The encoded protein is a member of the IL10 family of cytokines. It is a secreted protein and may function as a homodimer. This protein is thought to contribute to the transformed phenotype of T cells after infection by herpesvirus samimiri. [provided by RefSeq, Jul 2008]

IFNG-AS1 (HGNC:43910): (IFNG 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=0.13480118).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018402.2. 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
	IL26	NM_018402.2	MANE Select	c.284G>A	p.Gly95Asp	missense	Exon 3 of 5	NP_060872.1	Q9NPH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL26	ENST00000229134.5	TSL:1 MANE Select	c.284G>A	p.Gly95Asp	missense	Exon 3 of 5	ENSP00000229134.4	Q9NPH9
	IFNG-AS1	ENST00000536914.1	TSL:5	n.337-9301C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.25
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.030
Sift	Benign	0.31	T
Sift4G	Benign	0.10	T
Polyphen		0.11	B
Vest4		0.24
MutPred		0.46		Gain of disorder (P = 0.1065)
MVP		0.59
MPC		0.068
ClinPred		0.23	T
GERP RS		1.1
Varity_R		0.063
gMVP		0.21
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs767404352; hg19: chr12-68619008;