X-25013536-G-GGCGGCC
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The NM_139058.3(ARX):c.453_458dupGGCCGC(p.Ala152_Ala153dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 811,267 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_139058.3 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000478 AC: 5AN: 104588Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 29912
GnomAD4 exome AF: 0.0000226 AC: 16AN: 706679Hom.: 0 Cov.: 31 AF XY: 0.0000233 AC XY: 5AN XY: 214469
GnomAD4 genome AF: 0.0000478 AC: 5AN: 104588Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 29912
ClinVar
Submissions by phenotype
not provided Uncertain:2
Alanine repeat expansion in the second polyalanine tract of the ARX protein, extending the allele to 14 repeats; Polyalanine repeat expansions of 12 or fewer repeats have been observed in unaffected adult males undergoing testing at GeneDx; Polyalanine repeat expansions of 13-19 repeats have not been previously reported in the literature, to our knowledge (HGMD) -
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Intellectual disability, X-linked, with or without seizures, arx-related;C3463992:Developmental and epileptic encephalopathy, 1 Uncertain:1
This variant, c.453_458dup, results in the insertion of 2 amino acid(s) of the ARX protein (p.Ala154_Ala155dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ARX-related conditions. ClinVar contains an entry for this variant (Variation ID: 96456). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at