chr17-8312073-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173728.4(ARHGEF15):āc.34C>Gā(p.Pro12Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000694 in 144,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12T) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.34C>G | p.Pro12Ala | missense_variant | 2/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.34C>G | p.Pro12Ala | missense_variant | 2/16 | 1 | NM_173728.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000694 AC: 1AN: 144014Hom.: 0 Cov.: 28
GnomAD3 exomes AF: 0.0000138 AC: 3AN: 217432Hom.: 0 AF XY: 0.0000171 AC XY: 2AN XY: 117256
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000566 AC: 7AN: 1237354Hom.: 0 Cov.: 34 AF XY: 0.00000488 AC XY: 3AN XY: 614374
GnomAD4 genome AF: 0.00000694 AC: 1AN: 144014Hom.: 0 Cov.: 28 AF XY: 0.0000143 AC XY: 1AN XY: 69932
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 14, 2023 | ClinVar contains an entry for this variant (Variation ID: 530538). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 12 of the ARHGEF15 protein (p.Pro12Ala). This variant is present in population databases (rs150480540, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ARHGEF15-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at