rs398122854
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_139058.3(ARX):c.81C>G(p.Tyr27Ter) variant causes a stop gained 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 Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 24)
Consequence
ARX
NM_139058.3 stop_gained
NM_139058.3 stop_gained
Scores
2
2
1
Clinical Significance
Conservation
PhyloP100: 5.79
Genes affected
ARX (HGNC:18060): (aristaless related homeobox) This gene is a homeobox-containing gene expressed during development. The expressed protein contains two conserved domains, a C-peptide (or aristaless domain) and the prd-like class homeobox domain. It is a member of the group-II aristaless-related protein family whose members are expressed primarily in the central and/or peripheral nervous system. This gene is thought to be involved in CNS development. Expansion of a polyalanine tract and other mutations in this gene cause X-linked cognitive disability and epilepsy. [provided by RefSeq, Jul 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 79 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-25015657-G-C is Pathogenic according to our data. Variant chrX-25015657-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 29964.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARX | NM_139058.3 | c.81C>G | p.Tyr27Ter | stop_gained | 1/5 | ENST00000379044.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARX | ENST00000379044.5 | c.81C>G | p.Tyr27Ter | stop_gained | 1/5 | 1 | NM_139058.3 | P1 | |
ARX | ENST00000636609.1 | n.36-12C>G | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 5 | |||||
ARX | ENST00000637394.1 | n.68-12C>G | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
Cov.:
24
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 24
GnomAD4 genome
Cov.:
24
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2010 | - - |
Intellectual disability, X-linked, with or without seizures, arx-related Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Genomics England Pilot Project, Genomics England | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
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