rs1486076923
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_173728.4(ARHGEF15):c.62G>A(p.Arg21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,278,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21C) has been classified as Uncertain significance.
Frequency
Consequence
NM_173728.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.62G>A | p.Arg21His | missense_variant | 2/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.62G>A | p.Arg21His | missense_variant | 2/16 | 1 | NM_173728.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000508 AC: 4AN: 78760Hom.: 0 Cov.: 17
GnomAD4 exome AF: 0.00000667 AC: 8AN: 1199406Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 581450
GnomAD4 genome AF: 0.0000508 AC: 4AN: 78760Hom.: 0 Cov.: 17 AF XY: 0.0000534 AC XY: 2AN XY: 37420
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2022 | ClinVar contains an entry for this variant (Variation ID: 530493). This variant has not been reported in the literature in individuals affected with ARHGEF15-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 21 of the ARHGEF15 protein (p.Arg21His). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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