rs771433483
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173728.4(ARHGEF15):c.1715G>A(p.Arg572His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R572C) 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.1715G>A | p.Arg572His | missense_variant | 10/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.1715G>A | p.Arg572His | missense_variant | 10/16 | 1 | NM_173728.4 | P1 | |
ARHGEF15 | ENST00000421050.2 | c.1715G>A | p.Arg572His | missense_variant | 10/16 | 1 | P1 | ||
ENST00000458568.1 | n.228C>T | non_coding_transcript_exon_variant | 2/2 | 3 | |||||
ARHGEF15 | ENST00000647883.1 | c.1178G>A | p.Arg393His | missense_variant | 7/13 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251140Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135736
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461702Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727150
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74276
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 530513). This variant has not been reported in the literature in individuals affected with ARHGEF15-related conditions. This variant is present in population databases (rs771433483, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 572 of the ARHGEF15 protein (p.Arg572His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at