rs794727656
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_139058.3(ARX):c.1269C>T(p.His423His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,118,457 control chromosomes in the GnomAD database, including 1 homozygotes. There are 51 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_139058.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARX | ENST00000379044.5 | c.1269C>T | p.His423His | synonymous_variant | Exon 4 of 5 | 1 | NM_139058.3 | ENSP00000368332.4 | ||
ARX | ENST00000637993.1 | c.-121C>T | upstream_gene_variant | 5 | ENSP00000490122.1 |
Frequencies
GnomAD3 genomes AF: 0.0000627 AC: 7AN: 111614Hom.: 0 Cov.: 22 AF XY: 0.0000296 AC XY: 1AN XY: 33792
GnomAD3 exomes AF: 0.0000172 AC: 1AN: 58125Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 11683
GnomAD4 exome AF: 0.000144 AC: 145AN: 1006843Hom.: 1 Cov.: 32 AF XY: 0.000156 AC XY: 50AN XY: 320779
GnomAD4 genome AF: 0.0000627 AC: 7AN: 111614Hom.: 0 Cov.: 22 AF XY: 0.0000296 AC XY: 1AN XY: 33792
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
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ARX: BP4, BP7 -
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Intellectual disability, X-linked, with or without seizures, ARX-related;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at