rs763458576
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_139058.3(ARX):āc.708T>Cā(p.Asp236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,150,186 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 53 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00012 ( 0 hom., 4 hem., cov: 23)
Exomes š: 0.00016 ( 0 hom. 49 hem. )
Consequence
ARX
NM_139058.3 synonymous
NM_139058.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.849
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant X-25013287-A-G is Benign according to our data. Variant chrX-25013287-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 507718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.849 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARX | NM_139058.3 | c.708T>C | p.Asp236= | synonymous_variant | 2/5 | ENST00000379044.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARX | ENST00000379044.5 | c.708T>C | p.Asp236= | synonymous_variant | 2/5 | 1 | NM_139058.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000119 AC: 13AN: 108939Hom.: 0 Cov.: 23 AF XY: 0.000126 AC XY: 4AN XY: 31819
GnomAD3 genomes
?
AF:
AC:
13
AN:
108939
Hom.:
Cov.:
23
AF XY:
AC XY:
4
AN XY:
31819
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000700 AC: 7AN: 100045Hom.: 0 AF XY: 0.0000839 AC XY: 3AN XY: 35759
GnomAD3 exomes
AF:
AC:
7
AN:
100045
Hom.:
AF XY:
AC XY:
3
AN XY:
35759
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000157 AC: 163AN: 1041247Hom.: 0 Cov.: 31 AF XY: 0.000145 AC XY: 49AN XY: 338957
GnomAD4 exome
AF:
AC:
163
AN:
1041247
Hom.:
Cov.:
31
AF XY:
AC XY:
49
AN XY:
338957
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000119 AC: 13AN: 108939Hom.: 0 Cov.: 23 AF XY: 0.000126 AC XY: 4AN XY: 31819
GnomAD4 genome
?
AF:
AC:
13
AN:
108939
Hom.:
Cov.:
23
AF XY:
AC XY:
4
AN XY:
31819
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
ARX-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Intellectual disability, X-linked, with or without seizures, arx-related;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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