12-122173903-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001014336.2(IL31):​c.106G>A​(p.Asp36Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

IL31
NM_001014336.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.37
Variant links:
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)

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ACMG classification

Classification made for transcript

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=0.07267791).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL31NM_001014336.2 linkc.106G>A p.Asp36Asn missense_variant Exon 2 of 3 ENST00000377035.2 NP_001014358.1 Q6EBC2
LRRC43NM_152759.5 linkc.-406+6121C>T intron_variant Intron 1 of 11 NP_689972.3 Q8N309-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL31ENST00000377035.2 linkc.106G>A p.Asp36Asn missense_variant Exon 2 of 3 1 NM_001014336.2 ENSP00000366234.1 Q6EBC2
LRRC43ENST00000537729.5 linkc.-406+6121C>T intron_variant Intron 1 of 5 5 ENSP00000438751.1 F5H0N3

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.106G>A (p.D36N) 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 106, causing the aspartic acid (D) at amino acid position 36 to be replaced by an asparagine (N). 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
0.080
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.3
DANN
Benign
0.92
DEOGEN2
Benign
0.032
T
Eigen
Benign
-0.97
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.50
N
REVEL
Benign
0.014
Sift
Benign
0.13
T
Sift4G
Benign
0.074
T
Polyphen
0.40
B
Vest4
0.12
MutPred
0.21
Gain of catalytic residue at L31 (P = 0.0669);
MVP
0.22
MPC
1.0
ClinPred
0.12
T
GERP RS
1.3
Varity_R
0.053
gMVP
0.11

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: chr12-122658450; API