10-5963815-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002189.4(IL15RA):c.310C>T(p.Pro104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,550,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
IL15RA
NM_002189.4 missense
NM_002189.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 1.25
Genes affected
IL15RA (HGNC:5978): (interleukin 15 receptor subunit alpha) This gene encodes a cytokine receptor that specifically binds interleukin 15 (IL15) with high affinity. The receptors of IL15 and IL2 share two subunits, IL2R beta and IL2R gamma. This forms the basis of many overlapping biological activities of IL15 and IL2. The protein encoded by this gene is structurally related to IL2R alpha, an additional IL2-specific alpha subunit necessary for high affinity IL2 binding. Unlike IL2RA, IL15RA is capable of binding IL15 with high affinity independent of other subunits, which suggests distinct roles between IL15 and IL2. This receptor is reported to enhance cell proliferation and expression of apoptosis inhibitor BCL2L1/BCL2-XL and BCL2. Multiple alternatively spliced transcript variants of this gene have been reported.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
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=0.36615175).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL15RA | NM_002189.4 | c.310C>T | p.Pro104Ser | missense_variant | 3/7 | ENST00000379977.8 | |
LOC107984200 | XR_001747348.2 | n.1321-369G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL15RA | ENST00000379977.8 | c.310C>T | p.Pro104Ser | missense_variant | 3/7 | 1 | NM_002189.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000143 AC: 2AN: 1398078Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1AN XY: 694250
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.310C>T (p.P104S) alteration is located in exon 3 (coding exon 3) of the IL15RA gene. This alteration results from a C to T substitution at nucleotide position 310, causing the proline (P) at amino acid position 104 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;D;.;.;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M;.;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
.;.;D;.;.;D;.;.;D
REVEL
Benign
Sift
Benign
.;.;T;.;.;T;.;.;T
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.;.;.;.
Vest4
MutPred
0.28
.;.;Gain of phosphorylation at P104 (P = 0.0728);.;.;Gain of phosphorylation at P104 (P = 0.0728);.;.;.;
MVP
MPC
0.52
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at