rs554267583
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173728.4(ARHGEF15):c.854G>A(p.Arg285His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,610,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.854G>A | p.Arg285His | missense_variant | Exon 3 of 16 | ENST00000361926.8 | NP_776089.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 4AN: 151720Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249216Hom.: 0 AF XY: 0.0000593 AC XY: 8AN XY: 134946
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1459000Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13AN XY: 725986
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151832Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74168
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 285 of the ARHGEF15 protein (p.Arg285His). This variant is present in population databases (rs554267583, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ARHGEF15-related conditions. ClinVar contains an entry for this variant (Variation ID: 403966). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at