NM_000206.3:c.325G>C

Variant names:

• chrX-71110633-C-G
• rs17875899
• NM_000206.3:c.325G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000206.3(IL2RG):​c.325G>C​(p.Glu109Gln) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: IL2RG NM_000206.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

Genes affected

IL2RG (HGNC:6010): (interleukin 2 receptor subunit gamma) The protein encoded by this gene is an important signaling component of many interleukin receptors, including those of interleukin -2, -4, -7 and -21, and is thus referred to as the common gamma chain. Mutations in this gene cause X-linked severe combined immunodeficiency (XSCID), as well as X-linked combined immunodeficiency (XCID), a less severe immunodeficiency disorder. [provided by RefSeq, Mar 2010]

ENSG00000285171 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07621625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL2RG	NM_000206.3	c.325G>C	p.Glu109Gln	missense_variant	Exon 3 of 8	ENST00000374202.7	NP_000197.1
IL2RG	XM_047442089.1	c.325G>C	p.Glu109Gln	missense_variant	Exon 3 of 7		XP_047298045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL2RG	ENST00000374202.7	c.325G>C	p.Glu109Gln	missense_variant	Exon 3 of 8	1	NM_000206.3	ENSP00000363318.3
ENSG00000285171	ENST00000646505.1	n.325G>C		non_coding_transcript_exon_variant	Exon 3 of 12			ENSP00000496673.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	4.8
DANN	Benign	0.57
DEOGEN2	Uncertain	0.47	T;.;T
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.15	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.49	T;.;.
Polyphen		0.0080	B;.;.
Vest4		0.061
MutPred		0.21		Gain of catalytic residue at E109 (P = 0.1745);.;.;
MVP		0.75
MPC		0.59
ClinPred		0.032	T
GERP RS		1.5
Varity_R		0.22
gMVP		0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs17875899; hg19: chrX-70330483;