rs122461160
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_014271.4(IL1RAPL1):c.1377C>A(p.Tyr459Ter) variant causes a stop gained 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. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 23)
Consequence
IL1RAPL1
NM_014271.4 stop_gained
NM_014271.4 stop_gained
Scores
3
1
1
Clinical Significance
Conservation
PhyloP100: 1.63
Genes affected
IL1RAPL1 (HGNC:5996): (interleukin 1 receptor accessory protein like 1) The protein encoded by this gene is a member of the interleukin 1 receptor family and is similar to the interleukin 1 accessory proteins. This protein has an N-terminal signal peptide, three extracellular immunoglobulin Ig-like domains, a transmembrane domain, an intracellular Toll/IL-1R domain, and a long C-terminal tail which interacts with multiple signalling molecules. This gene is located at a region on chromosome X that is associated with a non-syndromic form of X-linked intellectual disability. Deletions and mutations in this gene were found in patients with intellectual disability. This gene is expressed at a high level in post-natal brain structures involved in the hippocampal memory system, which suggests a specialized role in the physiological processes underlying memory and learning abilities, and plays a role in synapse formation and stabilization. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.341 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-29955106-C-A is Pathogenic according to our data. Variant chrX-29955106-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 11480.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-29955106-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL1RAPL1 | NM_014271.4 | c.1377C>A | p.Tyr459Ter | stop_gained | 11/11 | ENST00000378993.6 | |
IL1RAPL1 | XM_017029240.2 | c.1377C>A | p.Tyr459Ter | stop_gained | 11/11 | ||
IL1RAPL1 | XM_017029241.2 | c.999C>A | p.Tyr333Ter | stop_gained | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL1RAPL1 | ENST00000378993.6 | c.1377C>A | p.Tyr459Ter | stop_gained | 11/11 | 1 | NM_014271.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Intellectual disability, X-linked 21 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at