12-122173962-C-T

Position:

• chr12-122173962-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001014336.2(IL31):​c.47G>A​(p.Cys16Tyr) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL31 NM_001014336.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

Genes affected

IL31 (HGNC:19372): (interleukin 31) IL31, which is made principally by activated Th2-type T cells, interacts with a heterodimeric receptor consisting of IL31RA (MIM 609510) and OSMR (MIM 601743) that is constitutively expressed on epithelial cells and keratinocytes. IL31 may be involved in the promotion of allergic skin disorders and in regulating other allergic diseases, such as asthma (Dillon et al., 2004 [PubMed 15184896]).[supplied by OMIM, Mar 2008]

LRRC43 (HGNC:28562): (leucine rich repeat containing 43)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL31	NM_001014336.2	c.47G>A	p.Cys16Tyr	missense_variant	2/3	ENST00000377035.2	NP_001014358.1
LRRC43	NM_152759.5	c.-406+6180C>T		intron_variant			NP_689972.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL31	ENST00000377035.2	c.47G>A	p.Cys16Tyr	missense_variant	2/3	1	NM_001014336.2	ENSP00000366234.1
LRRC43	ENST00000537729.5	c.-406+6180C>T		intron_variant		5		ENSP00000438751.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Nov 10, 2024

The c.47G>A (p.C16Y) alteration is located in exon 2 (coding exon 2) of the IL31 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the cysteine (C) at amino acid position 16 to be replaced by a tyrosine (Y). 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	0.51
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-9.2	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.65		Gain of catalytic residue at W21 (P = 0);
MVP		0.26
MPC		1.7
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.93
gMVP		0.51

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: chr12-122658509;