chr17-8312112-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_173728.4(ARHGEF15):c.73C>T(p.Pro25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,427,138 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 (★).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.73C>T | p.Pro25Ser | missense_variant | Exon 2 of 16 | ENST00000361926.8 | NP_776089.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 exomes AF: 0.00000861 AC: 2AN: 232282Hom.: 0 AF XY: 0.00000796 AC XY: 1AN XY: 125680
GnomAD4 exome AF: 0.00000140 AC: 2AN: 1427138Hom.: 0 Cov.: 38 AF XY: 0.00000141 AC XY: 1AN XY: 710184
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
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. 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"). ClinVar contains an entry for this variant (Variation ID: 1493247). This variant has not been reported in the literature in individuals affected with ARHGEF15-related conditions. This variant is present in population databases (rs757041347, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 25 of the ARHGEF15 protein (p.Pro25Ser). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at