X-118741134-A-T

Variant names:

• chrX-118741134-A-T
• NM_001560.3:c.206A>T

Variant summary

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

The NM_001560.3(IL13RA1):​c.206A>T​(p.His69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: IL13RA1 NM_001560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL13RA1	NM_001560.3	c.206A>T	p.His69Leu	missense_variant	Exon 2 of 11	ENST00000371666.8	NP_001551.1
IL13RA1	XM_047442096.1	c.206A>T	p.His69Leu	missense_variant	Exon 2 of 11		XP_047298052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL13RA1	ENST00000371666.8	c.206A>T	p.His69Leu	missense_variant	Exon 2 of 11	1	NM_001560.3	ENSP00000360730.3
IL13RA1	ENST00000371642.1	c.206A>T	p.His69Leu	missense_variant	Exon 2 of 6	1		ENSP00000360705.1
IL13RA1	ENST00000652600.1	c.200A>T	p.His67Leu	missense_variant	Exon 3 of 12			ENSP00000498980.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.206A>T (p.H69L) alteration is located in exon 2 (coding exon 2) of the IL13RA1 gene. This alteration results from a A to T substitution at nucleotide position 206, causing the histidine (H) at amino acid position 69 to be replaced by a leucine (L). 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	Benign	0.17
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T;.
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.55	P;.
Vest4		0.49
MutPred		0.63		Loss of disorder (P = 0.0655);Loss of disorder (P = 0.0655);
MVP		0.98
MPC		0.25
ClinPred		0.41	T
GERP RS		4.6
Varity_R		0.37
gMVP		0.52

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-117875097;