1-67169354-T-C

Variant names:

• chr1-67169354-T-C
• NM_144701.3:c.83T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_144701.3(IL23R):​c.83T>C​(p.Ile28Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL23R NM_144701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

Genes affected

IL23R (HGNC:19100): (interleukin 23 receptor) The protein encoded by this gene is a subunit of the receptor for IL23A/IL23. This protein pairs with the receptor molecule IL12RB1/IL12Rbeta1, and both are required for IL23A signaling. This protein associates constitutively with Janus kinase 2 (JAK2), and also binds to transcription activator STAT3 in a ligand-dependent manner. [provided by RefSeq, Jul 2008]

C1orf141 (HGNC:32044): (chromosome 1 open reading frame 141)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL23R	NM_144701.3	c.83T>C	p.Ile28Thr	missense_variant	Exon 3 of 11	ENST00000347310.10	NP_653302.2
IL23R	XM_011540790.4	c.83T>C	p.Ile28Thr	missense_variant	Exon 3 of 11		XP_011539092.1
IL23R	XM_011540791.4	c.83T>C	p.Ile28Thr	missense_variant	Exon 3 of 11		XP_011539093.1
IL23R	XM_047447227.1	c.83T>C	p.Ile28Thr	missense_variant	Exon 3 of 11		XP_047303183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL23R	ENST00000347310.10	c.83T>C	p.Ile28Thr	missense_variant	Exon 3 of 11	1	NM_144701.3	ENSP00000321345.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jan 18, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 28 of the IL23R protein (p.Ile28Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IL23R-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.2	N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.69		Loss of sheet (P = 0.0037);
MVP		0.90
MPC		0.58
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.71

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-67635037;