rs762341051
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173728.4(ARHGEF15):c.2092G>A(p.Val698Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,834 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. V698A) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.2092G>A | p.Val698Ile | missense_variant | 13/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.2092G>A | p.Val698Ile | missense_variant | 13/16 | 1 | NM_173728.4 | P1 | |
ARHGEF15 | ENST00000421050.2 | c.2092G>A | p.Val698Ile | missense_variant | 13/16 | 1 | P1 | ||
ARHGEF15 | ENST00000647883.1 | c.1555G>A | p.Val519Ile | missense_variant | 10/13 | ||||
ARHGEF15 | ENST00000582060.1 | n.155G>A | non_coding_transcript_exon_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152052Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251100Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135732
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727186
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74254
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2021 | This variant has not been reported in the literature in individuals with ARHGEF15-related disease. 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: "Benign"; Align-GVGD: "Class C25"). This variant is present in population databases (rs762341051, ExAC 0.01%). This sequence change replaces valine with isoleucine at codon 698 of the ARHGEF15 protein (p.Val698Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at