rs1060500048
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173728.4(ARHGEF15):c.1102delG(p.Val368TrpfsTer59) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_173728.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARHGEF15 | NM_173728.4 | c.1102delG | p.Val368TrpfsTer59 | frameshift_variant | Exon 6 of 16 | ENST00000361926.8 | NP_776089.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.1102delG | p.Val368TrpfsTer59 | frameshift_variant | Exon 6 of 16 | 1 | NM_173728.4 | ENSP00000355026.3 | ||
ARHGEF15 | ENST00000421050.2 | c.1102delG | p.Val368TrpfsTer59 | frameshift_variant | Exon 6 of 16 | 1 | ENSP00000412505.1 | |||
ARHGEF15 | ENST00000647883.1 | c.565delG | p.Val189TrpfsTer59 | frameshift_variant | Exon 3 of 13 | ENSP00000498197.1 | ||||
ARHGEF15 | ENST00000578286.1 | n.150delG | non_coding_transcript_exon_variant | Exon 2 of 3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461700Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727138
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ARHGEF15 cause disease. Therefore, this variant has been classified as a Variant of Uncertain Significance. 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 deletes 1 nucleotide from exon 6 of the ARHGEF15 mRNA (c.1102delG), causing a frameshift at codon 368. This creates a premature translational stop signal (p.Val368Trpfs*59) and is expected to result in an absent or disrupted protein product. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at