rs747885678
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173728.4(ARHGEF15):c.194C>T(p.Pro65Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,514,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.194C>T | p.Pro65Leu | missense_variant | 2/16 | ENST00000361926.8 | NP_776089.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000685 AC: 1AN: 145980Hom.: 0 Cov.: 24
GnomAD3 exomes AF: 0.0000190 AC: 4AN: 210976Hom.: 0 AF XY: 0.0000178 AC XY: 2AN XY: 112434
GnomAD4 exome AF: 0.0000102 AC: 14AN: 1368034Hom.: 0 Cov.: 36 AF XY: 0.0000103 AC XY: 7AN XY: 676832
GnomAD4 genome AF: 0.00000685 AC: 1AN: 145980Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 70816
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2023 | The c.194C>T (p.P65L) alteration is located in exon 2 (coding exon 1) of the ARHGEF15 gene. This alteration results from a C to T substitution at nucleotide position 194, causing the proline (P) at amino acid position 65 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 02, 2021 | 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"). This variant has not been reported in the literature in individuals with ARHGEF15-related disease. This variant is present in population databases (rs747885678, ExAC 0.003%). This sequence change replaces proline with leucine at codon 65 of the ARHGEF15 protein (p.Pro65Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at