X-25004738-CCTTGGCCTTGAGCCTCAGCGCGGCTATG-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_139058.3(ARX):c.1593_1620del(p.Ser531ArgfsTer117) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 24)
Consequence
ARX
NM_139058.3 frameshift
NM_139058.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.28
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 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 0.0568 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-25004738-CCTTGGCCTTGAGCCTCAGCGCGGCTATG-C is Pathogenic according to our data. Variant chrX-25004738-CCTTGGCCTTGAGCCTCAGCGCGGCTATG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 803780.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARX | NM_139058.3 | c.1593_1620del | p.Ser531ArgfsTer117 | frameshift_variant | 5/5 | ENST00000379044.5 | NP_620689.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARX | ENST00000379044.5 | c.1593_1620del | p.Ser531ArgfsTer117 | frameshift_variant | 5/5 | 1 | NM_139058.3 | ENSP00000368332 | P1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
Cov.:
24
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 24
GnomAD4 genome
Cov.:
24
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Corpus callosum agenesis-abnormal genitalia syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at