chr17-8312076-A-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_173728.4(ARHGEF15):c.37A>C(p.Thr13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. T13M) has been classified as Uncertain significance.
Frequency
Consequence
NM_173728.4 missense
Scores
Clinical Significance
Conservation
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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.37A>C | p.Thr13Pro | missense_variant | 2/16 | ENST00000361926.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARHGEF15 | ENST00000361926.8 | c.37A>C | p.Thr13Pro | missense_variant | 2/16 | 1 | NM_173728.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 68AN: 62216Hom.: 0 Cov.: 16 FAILED QC
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000527 AC: 530AN: 1006534Hom.: 0 Cov.: 33 AF XY: 0.000563 AC XY: 279AN XY: 495326
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00109 AC: 68AN: 62314Hom.: 0 Cov.: 16 AF XY: 0.000949 AC XY: 29AN XY: 30572
ClinVar
Submissions by phenotype
Early infantile epileptic encephalopathy with suppression bursts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 22, 2021 | This sequence change replaces threonine with proline at codon 13 of the ARHGEF15 protein (p.Thr13Pro). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and proline. This variant is not present in population databases (ExAC no frequency). 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 C0"). This variant has not been reported in the literature in individuals with ARHGEF15-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at