X-118776442-A-G

Position:

• chrX-118776442-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001560.3(IL13RA1):​c.1122A>G​(p.Ile374Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

Genes affected

IL13RA1 (HGNC:5974): (interleukin 13 receptor subunit alpha 1) The protein encoded by this gene is a subunit of the interleukin 13 receptor. This subunit forms a receptor complex with IL4 receptor alpha, a subunit shared by IL13 and IL4 receptors. This subunit serves as a primary IL13-binding subunit of the IL13 receptor, and may also be a component of IL4 receptors. This protein has been shown to bind tyrosine kinase TYK2, and thus may mediate the signaling processes that lead to the activation of JAK1, STAT3 and STAT6 induced by IL13 and IL4. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32141674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL13RA1	NM_001560.3	c.1122A>G	p.Ile374Met	missense_variant	10/11	ENST00000371666.8	NP_001551.1
IL13RA1	XM_047442096.1	c.1122A>G	p.Ile374Met	missense_variant	10/11		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL13RA1	ENST00000371666.8	c.1122A>G	p.Ile374Met	missense_variant	10/11	1	NM_001560.3	ENSP00000360730.3
IL13RA1	ENST00000652600.1	c.1116A>G	p.Ile372Met	missense_variant	11/12			ENSP00000498980.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 841914 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 240058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.1122A>G (p.I374M) alteration is located in exon 10 (coding exon 10) of the IL13RA1 gene. This alteration results from a A to G substitution at nucleotide position 1122, causing the isoleucine (I) at amino acid position 374 to be replaced by a methionine (M). 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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	-0.027	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.88	N
REVEL	Uncertain	0.42
Sift	Uncertain	0.029	D
Sift4G	Benign	0.081	T
Polyphen		0.31	B
Vest4		0.39
MutPred		0.73		Gain of sheet (P = 0.0085);
MVP		0.92
MPC		0.22
ClinPred		0.94	D
GERP RS		1.0
Varity_R		0.25
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-117910405;