rs1060500050
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_173728.4(ARHGEF15):c.491G>A(p.Arg164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,609,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R164W) has been classified as Uncertain significance.
Frequency
Consequence
NM_173728.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.491G>A | p.Arg164Gln | missense_variant | 2/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.491G>A | p.Arg164Gln | missense_variant | 2/16 | 1 | NM_173728.4 | P1 | |
ARHGEF15 | ENST00000421050.2 | c.491G>A | p.Arg164Gln | missense_variant | 2/16 | 1 | P1 | ||
ARHGEF15 | ENST00000579439.5 | c.491G>A | p.Arg164Gln | missense_variant | 2/3 | 5 | |||
ARHGEF15 | ENST00000455564.3 | n.604G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152076Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246220Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133162
GnomAD4 exome AF: 0.00000686 AC: 10AN: 1457910Hom.: 0 Cov.: 36 AF XY: 0.00000552 AC XY: 4AN XY: 725014
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152076Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74286
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 26, 2021 | The c.491G>A (p.R164Q) alteration is located in exon 2 (coding exon 1) of the ARHGEF15 gene. This alteration results from a G to A substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 to be replaced by a glutamine (Q). 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 | Invitae | Nov 30, 2016 | This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ARHGEF15-related disease. This sequence change replaces arginine with glutamine at codon 164 of the ARHGEF15 protein (p.Arg164Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at